Zeitschriftenartikel: „CYP2C19-polymorphisms“

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Mărginean, Alina, Claudia Bănescu, Valeriu Moldovan, Alina Scridon, Mihai Mărginean, Rodica Bălaşa, Smaranda Maier, Mariana Ţăruşi und Minodora Dobreanu. „The Impact of CYP2C19 Loss-of-Function Polymorphisms, Clinical, and Demographic Variables on Platelet Response to Clopidogrel Evaluated Using Impedance Aggregometry“. Clinical and Applied Thrombosis/Hemostasis 23, Nr. 3 (09.07.2016): 255–65. http://dx.doi.org/10.1177/1076029616629211.

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Introduction: Clopidogrel is an antiplatelet drug widely used in patients with acute coronary syndromes or stroke. Despite adequate antiplatelet therapy, some patients develop acute ischemic events. This is partly attributed to the fact that they have poor inhibition of platelet reactivity, despite treatment. This study aimed to assess the impact of clinical and demographic variables and of cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms on platelet response to clopidogrel evaluated using impedance aggregometry in an East European population. Methods: The study included 189 clopidogrel-treated patients with acute coronary syndromes and noncardiogenic ischemic stroke. Platelet aggregation was evaluated by impedance aggregometry. CYP2C19 loss-of-function polymorphisms were detected using the polymerase chain reaction restriction fragment length polymorphism technique. Various clinical and demographic data were also recorded. Results: In our data set, 81% of the patients were responders and 19% nonresponders to clopidogrel therapy. The distribution of CYP2C19 polymorphisms was as follows: 61.1% of patients were CYP2C19 wild-type homozygotes, 27.7% of patients were CYP2C19*2 heterozygotes, 1.1% of patients were CYP2C19*3 heterozygotes, and 10% of patients were CYP2C19*2 homozygotes. The highest level of association with clopidogrel response status was found for CYP2C19 polymorphisms, concomitant aspirin treatment, leukocyte and platelet count, history of myocardial infarction, arterial hypertension, and ward where patients were admitted. Conclusion: The prevalence of clopidogrel resistance in our East European population was in line with that reported for Western populations. Clopidogrel response was significantly influenced by the presence of CYP2C19 polymorphisms. Interestingly, the concomitant use of aspirin had a significant impact on platelet response to clopidogrel, indicating a synergic interaction between these drugs.

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SUZUKI, T., K. MATSUO, A. SAWAKI, K. WAKAI, K. HIROSE, H. ITO, T. SAITO et al. „Influence of smoking and CYP2C19 genotypes on H. pylori eradication success“. Epidemiology and Infection 135, Nr. 1 (02.06.2006): 171–76. http://dx.doi.org/10.1017/s0950268806006613.

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CYP2C19 polymorphisms and smoking influence the efficacy of H. pylori eradication therapy, but interaction between the two have hitherto not been examined. A total of 142 H. pylori-positive patients who received triple drug therapy with lansoprazole, amoxicillin and clarithromycin were categorized into three groups with regard to diplotypes of CYP2C19: homozygous extensive metabolizer (homEM), heterozygous EM (hetEM), and poor metabolizer (PM). The overall success rate was 61·3%. Smoking was an independent risk factor of eradication failure (OR 2·81, 95% CI 1·14–6·91), whereas CYP2C19 polymorphisms were less influential. Among non-smokers, the homEM and hetEM groups showed worse eradication rates (58·5 and 67·3%) relative to PM (76·2%) as expected; however, an opposite trend was observed among smokers (homEM 50·0%, hetEM 46·7%, PM 20·0%), indicating possible interactions with CYP2C19 polymorphisms. Smoking has a greater influence on H. pylori eradication than the CYP2C19 genotype. Interaction between smoking and CYP2C19 should be examined in the future.

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Angiolillo, Dominick J., Jose L. Ferreiro, Joseph A. Jakubowski, Kenneth J. Winters, Mark B. Effron, Suman Duvvuru, Timothy M. Costigan et al. „Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways“. Thrombosis and Haemostasis 110, Nr. 12 (2013): 1223–31. http://dx.doi.org/10.1160/th13-03-0263.

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SummaryClopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.

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Islam, Md Rabiul, Tasnova Tasnim Nova, NAM Momenuzzaman, Sikder Nahidul Islam Rabbi, Ishrat Jahan, Thomas Binder, Mohammad Safiqul Islam, Abul Hasnat und Zabun Nahar. „Prevalence of CYP2C19 and ITGB3 polymorphisms among Bangladeshi patients who underwent percutaneous coronary intervention“. SAGE Open Medicine 9 (Januar 2021): 205031212110422. http://dx.doi.org/10.1177/20503121211042209.

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Introduction: Antithrombotic agents are the basic therapeutic option for patients with arterial thrombosis who underwent percutaneous coronary intervention (PCI). In Bangladesh, aspirin and clopidogrel are frequently prescribed as antithrombotics or platelet inhibitors. Studies reported the genetic polymorphisms of CYP2C19*2, CYP2C19*17, and ITGB3 cause an alteration of the pharmacodynamic and pharmacokinetic profile of aspirin and clopidogrel. Therefore, we aimed to assess the prevalence of CYP2C19*2, CYP2C19*17, and ITGB3 polymorphisms among Bangladeshi patients with cardiovascular disease (CVD) who underwent PCI. Methods: Here we assessed a total of 1,000 CVD patients (male 782 and female 218) who underwent PCI and were treated with clopidogrel and/or aspirin. We performed genotyping of patients treated with clopidogrel and aspirin by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) methods. The PCR products of clopidogrel-treated patients were screened with agarose gel electrophoresis and then digested with SmaI and NsiI-HF for CYP2C19*2 and CYP2C19*17, respectively. We genotyped aspirin-treated patients with T-ARMS-PCR for missense rs5918 (PlA1/A1) polymorphism of the ITGB3 gene. Then we ran the digested PCR products on 2% agarose gel electrophoresis to detect the mentioned polymorphisms. Results: Among the clopidogrel-treated patients, we observed 64.1% polymorphism (hetero + mutant) of CYP2C19*2 (loss-of-function allele) and 22.7% (hetero + mutant) of CYP2C19*17 (gain-of-function allele). On the other hand, among the aspirin-treated patients, polymorphisms of ITGB3 were 84.1% homozygous (PlA1/A1), 15.6% heterozygous (PlA1/A2), and 0.3% mutant homozygous. Conclusion: In the present study, we observed a high prevalence of genetic polymorphisms of CYP2C19 and ITGB3 genes. Therefore, we recommend genotyping of CVD patients before prescribing clopidogrel or aspirin to prevent coagulation. Based on the genotyping study, the adjustment of doses or alternative generics might require to avoid therapeutic failure or toxicity in some cases.

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Riaz, Sana, Atika Mansoor, Saima Siddiqi, Muhammad Usman Tareen, Sana Rubab, Ayesha Batool, Anwarullah und Aneesa Sultan. „Association of CYP2C19*2 and *17 genetic variants with hypertension in Pakistani population“. Tropical Journal of Pharmaceutical Research 18, Nr. 4 (24.05.2021): 851–55. http://dx.doi.org/10.4314/tjpr.v18i4.24.

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Purpose: To investigate the association of *2 and *17 single nucleotide polymorphisms (SNPs) of CYP2C19 gene with hypertension in Pakistani population. Methods: The study was conducted on 527 hypertensive patients and 530 unrelated healthy controls from selected regions of Pakistan. DNA was extracted from leukocytes and all patients and controls were genotyped for two SNPs (rs4244285 and rs12248560) of CYP2C19 gene by allele specific polymerase chain reaction (AS-PCR). Results: Multi-allelic polymorphism in CYP2C19 identified four distinct phenotypes known as ultra-rapid metabolizer (UM), extensive metabolizer (EM), intermediate metabolizer (IM) and poor metabolizer (PM) in hypertensive patients and controls. For CYP2C19*2 polymorphisms, overall wild type and mutant allele frequency were 75 and 25 % in hypertensive patients, and 64.2 and 35.8 % in controls. For CYP2C19*17 polymorphisms, the overall wild type and mutant allele frequency were 66.6 and 33.4 % in hypertensive patients and 75.6 % and 24.4 % in controls. Significant difference in allele frequencies for CYP2C19*2 and *17 was demonstrated between hypertensive and non-hypertensive subjects. Conclusion: To the best of our knowledge, this is the first report on CYP2C19 frequencies in hypertensive Pakistani patients. The finds should help clinicians to determine a suitable optimal dosage of some drugs in order to reduce side effects.

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Tantsura, Lyudmyla, Olena Pylypets, Yevhen Tantsura und Dmytro Tretiakov. „Possibilities of optimizing approaches to the treatment of resistant epilepsy in children using pharmacogenetic studies data“. Ukrains'kyi Visnyk Psykhonevrolohii 27, Nr. 3 (05.09.2019): 92–96. http://dx.doi.org/10.36927/2079-0325-v27-is3-2019-18.

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We conducted an observation of 83 children with therapy-resistant forms of epilepsy between the ages of 11 months and 18 years. The presence of CYP2C9, CYP2C19 and CYP3A4 gene polymorphisms was detected in 60 of the examined patients, that is, 72.29 % of them, 33 patients (39.76 %) had CYP2C19 gene polymorphisms, CYP2C9 gene polymorphisms had 17 (20.48 %) children, and 10 (12.05 %) of them had CYP3A4 gene polymorphisms. The frequency of CYP2C19*2 and CYP3A4*1B polymorphisms was signifi cantly higher than in the Ukrainian and other European populations, no statistical data signifi - cance of differences in the frequency of CYP2C9 gene polymorphisms compared with the Ukrainian population was found. CYP2C19 gene polymorphisms are signifi cantly more frequently recorded by us compared to the results obtained by researchers in Russia and Turkey in closely related studies. It is shown that children with cytochrome P450 gene polymorphisms are recommended: more frequent clinical, instrumental, and laboratory monitoring of patients to prevent side eff ects of therapy; monitoring (not a one-time study) of AED concentration in blood plasma. The necessity of conduction of pharmacogenetic research at the stage of debut of epilepsy in the case of suspicion of treatment-resistant form of the disease and in the case of ineffi - ciency or severe side eff ects of the fi rst assigned AED was demonstrated. Key words: children, treatment, resistant epilepsy, cytochrome P450, gene polymorphism.

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Arévalo-Galvis, Azucena, William A. Otero-Regino, Gloria N. Ovalle-Celis, Eliana R. Rodríguez-Gómez und Alba A. Trespalacios-Rangel. „Prevalence of CYP2C19 polymorphism in Bogotá, Colombia: The first report of allele *17“. PLOS ONE 16, Nr. 1 (27.01.2021): e0245401. http://dx.doi.org/10.1371/journal.pone.0245401.

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Introduction Proton pump inhibitors (PPIs) are a group of drugs that are essential for the treatment of acid-related disorders, such as gastroesophageal reflux (GERD), dyspepsia, gastric ulcers and Helicobacter pylori (H. pylori) infection. PPIs such as omeprazole, esomeprazole, pantoprazole and lansoprazole are metabolized by the CYP2C19 enzyme, which is encoded by a polymorphic gene. Four polymorphisms have an impact on the speed of PPI metabolism: CYP2C19*1/*1 (extensive metabolizers), CYP2C19*2/*2 (intermediate metabolizers), CYP2C19*3/*3 (poor metabolizers) and CYP2C19*17/*17 (ultrarapid metabolizers). Extensive and ultrarapid metabolizers inactivate PPIs quickly, which consequently causes low plasma concentrations of PPIs, while intermediate or poor metabolizers have higher plasma concentrations of PPIs and, therefore, PPIs have greater therapeutic efficacy in individuals with these polymorphisms. Objective To determine the frequency of genetic polymorphisms of the CPY2C19 enzyme in Bogotá, Colombia. Methods This observational study was conducted in Bogotá between 2012 and 2015 and was part of a clinical trial (ID: NCT03650543). It included 239 subjects with dyspepsia, H. pylori infection, or GERD symptoms. CYP2C19 genotyping was performed on gastric biopsy samples. Polymorphisms *1, *2, and *3 were analyzed by real-time PCR (Roche®), and PCR-RFLP was used to determine the presence of polymorphism *17. Results The distribution of different types of PPI metabolizers was as follows: extensive (70.7%), ultrarapid (12.9%), intermediate (8.8%) and poor (0.8%). Conclusion The population studied consisted mainly of extensive and ultrarapid PPI metabolizers. These findings show that it is necessary to increase PPI doses in this group of subjects or to use PPIs that are not metabolized by CYP2C19 (rabeprazole). This is the first Colombian work to identify ultrarapid metabolizers.

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Song, Yan, Miao-xin Jia, Guang Yang, Xin-yuan Feng, Dong-hong Yin, Jian-bang Kang, Qiang Zhao und Jin-ju Duan. „Association of CYP2C19 and UGT1A4 polymorphisms with voriconazole-induced liver injury“. Personalized Medicine 17, Nr. 1 (Januar 2020): 15–22. http://dx.doi.org/10.2217/pme-2019-0042.

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Aim: This study investigated the association between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4. Materials & methods: Thirty-eight adult patients who received voriconazole therapy were included in the study. Genotype of CYP2C19 was detected using gene chip hybrid analysis. The UGT1A4 142T>G was genotyped using PCR-RFLP analysis. Results: Ten patients (26.3%) had voriconazole-induced liver injury and were considered as the case group There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2 and UGT1A4 142T>G (p > 0.05), however, the GA frequency of CYP2C19 *3 in the drug-induced liver injury case group was higher than that in the control group (p < 0.05). Compared with patients carrying *1/*1 or *1/*2, there was no significant difference in voriconazole trough concentration of the patients with *1/*3 (p > 0.05). Conclusion: There was no significant correlation between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4.

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Kim, In-Suk, Young-Hoon Jeong und Gyeong-Won Lee. „CYP2C19*2 and *3 Polymorphisms Are Associated with High Post- Treatment Platelet Reactivity in Korean Patients with Acute Coronary Syndrome Undergoing Percutanous Coronary Intervention.“ Blood 112, Nr. 11 (16.11.2008): 982. http://dx.doi.org/10.1182/blood.v112.11.982.982.

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Abstract Background: Cytochrome P450 (CYP) 2C19 is an enzyme showing genetic polymorphism that may cause marked interindividual and interethnic variation in the metabolism and disposition of its substrates. CYP2C19*2 and CYP2C19*3 are the most common of CYP2C19 polymorphisms, and show phenotypic poor metabolism. Recent data have shown that the CYP2C19*2 loss-of-function allele is associated with a marked decrease in platelet response to clopidogrel in healthy controls and Caucasian patients with acute coronary syndrome. However, It is unknown whether CYP2C19 *3, which is frequently noted in Asian, is also associated with platelet response to clopidogrel. Therefore, this study was conducted to analyze the effect of CYP2C19 *2 and *3 polymorphisms on high post-treatment platelet reactivity (HPPR) on clopidogrel in Korean patients with acute coronary syndrome, as a representative of Asian populations. Methods: The study included 136 consecutive patients undergoing percutanous coronary intervention (PCI). Adenosine diphosphate (ADP)-induced platelet aggregation by light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay (Ultegra rapid platelet function assay; Accumetrics Inc., USA) were assessed after a loading dose and after the maintenance dose of clopidogrel before discharge. CYP2C19 genotype was analyzed by Snapshot method. Results: The genotypic distributions of CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, and *2/*3 were 57 (41.9%), 47 (34.6%), 12 (8.8%), 14 (10.3%), 6 (4.4%), and 6(4.4%), respectively. The frequencies of CYP2C19 mutant alleles in Korean were higher than Caucasians. The CYP2C19*2 and CYP2C19*3 polymorphisms were significantly associated with persistent higher platelet aggregation by LTA, and lower inhibition of platelet reactivity by VerifyNow P2Y12 assay after clopidogrel than CYP2C19*1 genotype. The CYP2C19*2 and *3 alleles were more frequent in clopidogrel hyporesponsiveness, defined by persistent HPPR (5 uM ADP-induced platelet aggregation >50%; p = 0.01). Conclusions: This study suggests that the CYPC19*2 and *3 alleles influence clopidogrel hyporesponsiveness after clopidogrel in Asian patients with acute coronary syndromes undergoing PCI. These findings can have a significant impact on the future design of pharmacognetic antiaggregant strategies for acute coronary syndrome on antiplatelet treatment.

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Golubeva, T. S., T. V. Dokukina, V. G. Objedkov, S. I. Osipchik, T. V. Korotkevich, A. A. Gilep, I. V. Gaidukevich et al. „GENETIC MARKERS OF PHARMACORESISTANCE IN SCHIZOPHRENIA“. Medical Journal, Nr. 2(75) (2021): 62–69. http://dx.doi.org/10.51922/1818-426x.2021.2.62.

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The study of genetic markers of pharmacoresistance in schizophrenia, significant for the population of the Republic of Belarus, such as polymorphisms CYP2D6*4, CYP2C19*2, CYP2C19*17, CYPU2*F, С3435Т MDR1, TaqI ANKK1, d019G mRM, Val158Met СОМТ, Val66Met BDNF, C957T DRD2 was implemented. The possibilities of their use in predicting an adverse pharmacological response were described. Data on the use of genetic markers to determine the tactics of treating patients with schizophrenia were obtained; the sensitivity and specificity of the pharmacogenetic test for each marker were calculated. Specific genetic markers, such as polymorphisms CYP2D6*4, CYP2C19*2, CYP2C19*17, CYP1A2*F, C3435T MDR1, TaqI ANKK1, have been identified, which should be preferred for inclusion in diagnostic panels when predicting an adverse pharmacological response in the treatment of schizophrenia.

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Ivashchenko, D. V., K. A. Ryzhikova, Zh A. Sozaeva, Y. A. Pimenova, E. A. Grishina, M. S. Zastrozhin, A. D. Aguzarov, L. M. Savchenko, E. A. Bryun und D. A. Sychev. „IMPACT OF CYP3A5, CYP2C9, CYP2C19, AND CYP2D6 POLYMORPHISMS ON PHENAZEPAM SAFETY IN PATIENTS WITH ALCOHOL WITHDRAWAL SYNDROME“. Annals of the Russian academy of medical sciences 73, Nr. 3 (09.07.2018): 206–14. http://dx.doi.org/10.15690/vramn989.

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Introduction: Phenazepam is the Russian original benzodiazepine tranquilizer. We conducted first pharmacogenetic study on Phenazepam’s safety in patients with alcohol withdrawal syndrome. Isoenzymes CYP3A4, CYP3A5, CYP2C9, and CYP2C19 are involved into benzodiazepine tranquilizers’ metabolism.Aim: To determine predictive value of CYP3A5, CYP2C9, CYP2C19, and CYP2D6 genetic polymorphisms and their haplotypes for adverse reaction risk associated with the treatment with phenazepam.Materials and methods: The study enrolled 102 male patients with non-comlicated alcohol withdrawal syndrome (F10.3 by ICD-10) who entered the study group in 24 hours after the admission to hospital and was administered Phenazepam for 6 days. Therapy safety was evaluated with UKU Side Effects Rating Scale on the 6th day of treatment. 5 ml of venous blood was collected from each participant for genotyping to detect CYP3A5*3, CYP2С9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2C19*17, and CYP2D6*4 polymorphisms by real-time polymerase chain reaction. Haplotype analysis was performed by SNPStats online-tool. Statistical analysis was made in SPSS Statistics 21.0.Results: In overall sample (n=102) CYP2C9*3 increased risk of «Increased duration of sleep» (OR 1.46; 95% CI 1.11−1.9; p=0.037) and «Constipation» (OR 13.1; 95% CI 1.44−119.2; p=0.02). The following results in subgroup «Phenazepam’s monotherapy» (n=64) were observed: CYP3A5*3 increased global severity of adverse drug reactions according to patient’s opinion (OR 2.79; 95% CI 1.26−6.22; p=0.031); CYP2C9*3 led to «Increased duration of sleep» (OR 1.57; 95% CI 1.14−2.17; p=0.034). Haplotype CYP3A5*3-CYP2C19*2-CYP2C19*17 (G-G-T) was associated with increased risk of «Concentration difficulties (OR 2.86; 95% CI 0.96−8.50; p=0.061).Conclusion: The study findings confirmed that CYP2C9*3, CYP3A5*3, and CYP2C19*2 polymorphisms can decrease the phenazepam safety rate in patients with alcohol withdrawal syndrome. The result of haplotype analysis revealed that only CYP3A5*3-CYP2C19*2-CYP2C19*17 (G-G-T) can be used as a significant predictor of adverse reaction to phenazepam.

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Mirzaev, Karin B., Eric Rytkin, Kristina A. Ryzhikova, Elena A. Grishina, Zhannet A. Sozaeva, Denis S. Fedorinov, Olga D. Konova et al. „The ABCB1, CYP2C19, CYP3A5 and CYP4F2 genetic polymorphisms and platelet reactivity in the early phases of acute coronary syndromes“. Drug Metabolism and Personalized Therapy 33, Nr. 3 (25.09.2018): 109–18. http://dx.doi.org/10.1515/dmpt-2018-0006.

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Abstract Background The aim was to study seven polymorphic markers of genes encoding proteins involved in the absorption, metabolism and pharmacokinetics of clopidogrel among patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Methods Eighty-one ACS and PCI patients older than 18 years and treated with dual antiplatelet therapy were enrolled in the study. Platelet function testing and ABCB1, CYP2C19, CYP3A5 and CYP4F2 genotyping were performed. The predictive role of categorical variables, such as genotypes (carriers and non-carriers of polymorphism), on platelet reactivity (platelet reactivity units [PRU] platelet inhibition [PI]) was assessed by logistic regression (for categorical outcomes) and linear regression (for continuous outcomes) analysis. A p-value<0.05 was considered significant. The allele frequencies were estimated by gene counting, and Hardy-Weinberg equilibrium was tested using the chi-square test. Results Regarding clopidogrel response, 62 patients (76.5%) were clopidogrel responders and 19 were non-responders (23.5%). Mean PRU value and the percentage of platelet inhibition were 170.0±50.9 PRU and 28.6±19.9%, respectively. The effects of the CYP2C19*2 polymorphisms on PRU (166.0±50.8 vs. 190.7±48.2, p<0.038) and PI (30.6±20.0 vs. 18.1±16.3, p<0.013) were observed, and the rates of high platelet reactivity (HPR) were lower in CYP2C19*1/*1 than those in CYP2C19*1/*2+CYP2C19*2/*2 (16.2% vs. 53.8% p<0.0067). In comparison, no significant difference in PRU value and PI was observed at <5 days between the rest of polymorphisms (p>0.05). Based on the logistic regression analysis, CYP2C19*2 (OR: 4.365, CI: 1.25–17.67, p=0.022) was an independent predictor of HPR at <5 days, as was the stent diameter (OR: 0.219, CI: 0.002–0.229, p=0.049). The remaining polymorphisms had no influence. Conclusions The reactivity of the on-clopidogrel platelet in the early phase of ACS is influenced primarily by the CYP2C19 polymorphisms. We believe that the findings of the present study could supply additional evidence regarding the clinical appropriateness of the CYP2C19 genetic testing for designing suitable antiplatelet therapy in the early phase of ACS.

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Triwani, Triwani, und Lusia Hayati. „Prevalence of CYP2C19 Gene Polymorphism and Its Influence In Omeprazole Metabolism As Predictors Of Drug Inoxification In Malay Ethnic In South Sumatra“. SRIWIJAYA JOURNAL OF MEDICINE 1, Nr. 2 (30.04.2018): 108–14. http://dx.doi.org/10.32539/sjm.v1i2.15.

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Cytochrome P450 2C19 (CYP2C19) is an enzyme complex that plays a role in the metabolism of several drugs and is part of the super family of cytochrome P450. Genetic polymorphisms in these enzymes are associated with the emergence of poor metabolic phenotypes (poor metabolizers / PMs and intermediate metabolizers / IMs) that have a poor ability to metabolize the drugs that become substrates. Genotypes and phenotypes were analyzed using PCR-RFLP and bio-analysis of omeprazole levels in 30 subjects from ethnic Malay living in South Sumatra. Markers used to assess the presence of polymorphisms in the CYP2C19 gene are two polymorphic sites of exon 5 (CYP2C19 * 2) and exon 4 (CYP2C19 * 3). 321 bp DNA bands for exon 5 and 271 bp for exon 4 will be produced after DNA amplification by PCR method under denaturation for 5 min at 95oC; followed by 60 seconds at 95oC, 60sec at 53oC and 60sec at 72oC for 30 cycles; as well as the final polymerization for 5 minutes at 72 ° C. Furthermore, DNA cutting was done using the restriction enzyme endonuclease SmaI (CYP2C19 * 2) at 30oC and BamHI (CYP2C19 * 3) with incubation at 37oC for 3 hours. Bioanalysis of omeprazole levels in the blood with LC-MS. The results of this study indicate the presence of polymorphisms on both sites will eliminate the enzyme sites SmaI and BamHI. The results showed that 46.7% of South Sumatran Malay populations were classified as PM consisting of 13.3% homozygous mutandan mutant 33.4% heterozygotes. The high phenotype of PM enzyme CYP2C19 in ethnic Malays in South Sumatra predicted to influence metabolism of drugs become substrates. However, based on spearman correlation analysis, the correlation value was 0.035 with p = 0.875. This means that between the CYP2C19 gene polymorphism and the omeprazole levels in the blood there is a weak and meaningless correlation. The results of this study provide an overview of the high genetic polymorphisms of dyspepsia syndrome patients from the Malay population, ie almost half of the study subjects (46.7%). There is a weak and insignificant correlation between polymorphism and omeprazole levels.

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Ngo, Duy Anh, Trung Thien Tran, Anh Tuan Nguyen und Thanh Tien Nguyen. „APPLICATION OF THE REAL – TIME PCR FOR THE DETECTION OF CYP2C19*2 SINGLE NUCLEOTIDE POLYMORPHISM IN PATIENS WITH GASTRITIS AT TRA VINH GENERAL HOSPITAL“. Scientific Journal of Tra Vinh University 1, Nr. 32 (01.12.2018): 39–43. http://dx.doi.org/10.35382/18594816.1.32.2018.57.

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The aim of this study is to identify CYP2C19*2 single nucleotide polymorphisms in patients with gastritis at TraVinh General Hospital. A cross-sectional study was conducted in 280 endoscopic gastric biopsy samples of patients with gastritis at TraVinh General Hospital. CYP2C19*2 genotypes were determined by realtime PCR method using TaqMan probes. Data were stored and analyzed by IBM SPSS Statistic (version 20.0; Armonk, New York, USA) and Excel 2010. The prevallelece of GG, AG and AA genotypes were 51.8, 39.6 and 8.6% correspondingly. The ratio of allele G and A were 0.716 and 0.284 respectively. The correlation of CYP2C19*2 polymorphisms with age (p=0.891), gender (p=0.652) was not significantly distinguished

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Siasos, Gerasimos, Evangelos Oikonomou, Manolis Vavuranakis, Eleni Kokkou, Konstantinos Mourouzis, Sotiris Tsalamandris, Marina Zaromitidou et al. „Genotyping, Platelet Activation, and Cardiovascular Outcome in Patients after Percutaneous Coronary Intervention: Two Pieces of the Puzzle of Clopidogrel Resistance“. Cardiology 137, Nr. 2 (2017): 104–13. http://dx.doi.org/10.1159/000457947.

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Objectives: Individual platelet responses to antiplatelet therapy depend on genetic, cellular, and clinical factors. CYP2C19 and P2Y12 receptor polymorphisms are implicated in platelet responses to antiplatelet treatment. We aimed to evaluate the impact of CYP2C19 and C34T P2Y12 genotyping on platelet reactivity and cardiovascular outcome in patients after percutaneous coronary intervention (PCI) on clopidogrel treatment. Methods: We enrolled 408 patients with stable coronary artery disease (CAD) receiving aspirin and clopidogrel (75 mg/day) 1 month after PCI. High on-treatment platelet reactivity was evaluated using the VerifyNow Assay in a subset of patients. CYP2C19*2 and C34T P2Y12 genotyping was performed by real-time polymerase chain reaction. The primary end point was the composite of death or hospitalization for cardiovascular causes, and patients were followed for a median time of 13 months. Results: In the total study population, 37% were carriers of at least 1 CYP2C19*2 loss-of-function allele, and 53% were carriers of at least 1 C34T loss-of-function allele. Interestingly, homozygotes of the CYP2C19*2 loss-of-function allele had significantly increased P2Y12 reaction units (PRU) (p = 0.007). However, PRU did not differ between carriers and noncarriers of the C34T loss-of-function allele (p = 0.41). Moreover, carriers of CYP2C19*2 had an increased hazard ratio (HR) for the occurrence of the primary end point (for carriers HR = 1.96, 95% CI 1.05-3.66, p = 0.03), whereas the C34T polymorphism had no impact on the cardiovascular outcome (p = 0.17). Finally, PRU was associated with cardiovascular outcome even after adjustment for the presence of any reduced function allele polymorphism. Conclusions: We documented a different effect of CYP2C19 and P2Y12 receptor polymorphisms on platelet reactivity and cardiovascular outcome in CAD patients after PCI on clopidogrel treatment. Importantly, increased platelet reactivity adversely affects the cardiovascular outcome independently of the studied polymorphisms.

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Chen, B. L., Y. Chen, J. H. Tu, Y. L. Li, W. Zhang, Q. Li, L. Fan et al. „Clopidogrel Inhibits CYP2C19-Dependent Hydroxylation of Omeprazole Related to CYP2C19 Genetic Polymorphisms“. Journal of Clinical Pharmacology 49, Nr. 5 (Mai 2009): 574–81. http://dx.doi.org/10.1177/0091270009333016.

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Ivashchenko, Dmitriy V., Kristina A. Ryzhykova, Zhannet A. Sozaeva, Mikhail S. Zastrozhin, Elena A. Grishina, Lyudmila M. Savchenko, Eugeniy A. Bryun und Dmitriy A. Sychev. „Pharmacogenetic evaluation of adverse events’ risk in patients with alcohol withdrawal syndrome taking bromdihydrochlorphenylbenzodiazepine: The role of CYP2C19 gene polymorphisms“. World Journal of Personalized Medicine 1, Nr. 1 (03.11.2017): 18–26. http://dx.doi.org/10.14341/wjpm9262.

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Introduction. Bromdihydrochlorphenylbenzodiazepine is the Russian original tranquilizer which widely using in psychiatry, narcology, neurology and general medicine. Particularly, that drug prescribing for patients with alcohol withdrawal syndrome (AWS). Isoenzyme CYP2C19 takes part in metabolism of the most of benzodiazepines, so the gene CYP2C19 might be included into pharmacogenetics study of bromdihydrochlorphenylbenzodiazepine. There was no study of CYP2C19 polymorphisms as biomarkers of bromdihydrochlorphenylbenzodiazepine’s safety. Methods. 102 male patients with non-comlicated AWS (F 10.3 by ICD-10) were involved into the study. During 6 days of dynamic observation each participant was prescribed bromdihydrochlorphenylbenzodiazepine (Phenazepam). 5 ml of venous blood was collected from each participant for genotyping. 38 participants were added Pagluferal (contains phenobarbitalum, natrium coffeine-benzoate, bromisoval, papaverine) and/or Carbamazepine. Blood samples were analyzed to detect the CYP2C19*2 (rs4244285), *3 (rs4986893) и *17 (rs12248560) polymorphisms. Safety of therapy was evaluated with UKU Side Effects Rating Scale. Data analysis was performed with SPSS Statistics 21.0. Results. Carriers of CYP2C19*2 GA+AA genotypes compared to GG homozygous significantly more often had such adverse effects as «Polyuria/polydipsia» in mean grade of penetration (33,3% vs 9%, p=0,016) and “Palpitations/Tachycardia” (16,7% vs 3,8%, p=0,018). Observed relationship between «Polyuria/polydipsia» and CYP2C19*2 GA+AA genotypes was confirmed in the subgroup “Combined pharmacotherapy” (37,5% vs 0%, p=0,006). CYP2C19*17 polymorphism in tendency to significance was associated with less frequent AE «Polyuria/polydipsia» among patients taking bromdihydrochlorphenylbenzodiazepine as monotherapy carriers of allele T had that AE in 16,9%, and CC homozygous in 24,2% (p=0,067). Conclusion. Significant associations between CYP2C19*2 polymorphism and several AE in patients with alcohol withdrawal syndrome taking bromdihydrochlorphenylbenzodiazepine. Substantial role of CYP2C19*17 as predictor of AE associated with bromdihydrochlorphenylbenzodiazepine was not confirmed. Gene CYP2C19 is the sufficient biomarker of bromdihydrochlorphenylbenzodiazepine’s safety profile and needs further research.

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Suan, D., K. O'Connor, D. R. Booth, C. Liddle und G. J. Stewart. „Voriconazole toxicity related to polymorphisms in CYP2C19“. Internal Medicine Journal 41, Nr. 4 (April 2011): 364–65. http://dx.doi.org/10.1111/j.1445-5994.2011.02454.x.

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Krasniqi, Valon, Aleksandar Dimovski, Hasime Qorraj Bytyqi, Aleksandar Eftimov, Livija Šimičević und Nada Božina. „Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population“. Archives of Industrial Hygiene and Toxicology 68, Nr. 3 (26.09.2017): 180–84. http://dx.doi.org/10.1515/aiht-2017-68-2998.

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Abstract Cytochrome P450 genetic polymorphisms are responsible for individual variations in drug metabolism and drug-drug interactions. They are very important for pharmacogenetics, and their frequency varies across different populations. There is a big gap in the knowledge about the CYP gene family polymorphisms in the population of Kosovo, and the aim of our study was to fill that gap by determining the frequency of the most important variant alleles of CYP2C9, CYP2C19, and CYP3A5 in 234 nonrelated Kosovars. The allele frequencies of CYP2C9*2 and 2C9*3 were 17.52 %, and 10.89 %, respectively. Sixteen participants (6.81 %) were CYP2C9 poor metabolisers. The CYP2C19*2 and *17 variant frequencies were 13.03 % and 19.01 %, respectively. There were 2.13 % CYP2C19 poor and 4.27 % ultra-rapid metabolisers (homozygous carriers of the *17 allele). With regard to CYP3A5, the frequency of the *3 variant allele was 98.29 % (non-expressors), while the remaining participants (1.70 %) were expressors of CYP3A5. These findings are comparable with other European ethnicities, specifically those of Southeast Europe.

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Ge, Huijian, Xianli Lv, Hui Ren, Hengwei Jin, Yuhua Jiang, Hongwei He, Peng Liu und Youxiang Li. „Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling“. Journal of NeuroInterventional Surgery 9, Nr. 10 (15.09.2016): 958–62. http://dx.doi.org/10.1136/neurintsurg-2016-012635.

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ObjectiveTo investigate the influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling.MethodsBetween September 2014 and October 2015, we prospectively recruited 215 patients with intracranial aneurysms who were treated with stent-assisted coiling. CYP2C19 genotypes were determined and clopidogrel response was tested. The primary endpoints included symptomatic or silent ischemic events, and bleeding events. The secondary endpoint was clinical outcome at 3 months.ResultsOf the 215 patients, 108 (50.2%) were classified as intermediate metabolizers (IMs, CYP2C19*1/*2, *1/*3), 76 (35.3%) as extensive metabolizers (EMs, CYP2C19*1/*1) and 31 (14.4%) as poor metabolizers (PMs, CYP2C19*2/*2, *2/*3, *3/*3). Carriers of CYP2C19 loss-of-function (LOF) alleles (*2 or *3, p=0.001), especially PMs (p=0.004), had an increased risk for clopidogrel resistance. After the procedures, cerebral ischemic events occurred in 69 patients (32.1%) and bleeding was seen in 20 patients (9.3%). In comparison with IMs and PMs, EMs had a lower risk for ischemic events (21.1% vs 37.0% and 41.9%, p=0.02 and 0.027, respectively) and a relatively higher risk for bleeding events (18.4% vs 5.6% and 0%, p=0.006 and 0.01, respectively). Based on multivariate analysis, the carriage of CYP2C19 LOF alleles (p=0.032) and clopidogrel resistance (p=0.047) were considered as predictors of cerebral ischemic events, and EMs were significantly associated with bleeding (p=0.002). Posterior circulation aneurysms (p=0.038), hemorrhagic history (p=0.001) and poor metabolic genotypes (p=0.001) could result in poor clinical outcomes (modified Rankin Scale >2).ConclusionsCYP2C19 genetic polymorphisms had significant influence on the antiplatelet effect of clopidogrel, and could be considered as risk factors of ischemic or bleeding events and even clinical outcomes of patients with intracranial aneurysms treated with stent-assisted coiling.

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Devendran, Anichavezhi, Chakradhara Rao Satyanarayana Uppugunduri, Rajan Sundaram, Deepak Gopal Shewade, Krishnamoorthy Rajagopal und Adithan Chandrasekaran. „Relative Copy Number Variations of CYP2C19 in South Indian Population“. Molecular Biology International 2012 (25.06.2012): 1–4. http://dx.doi.org/10.1155/2012/643856.

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CYP2C19 is a polymorphic enzyme involved in the metabolism of clinically important drugs. Genotype-phenotype association studies of CYP2C19 have reported wide ranges in the metabolic ratios of its substrates. These discrepancies could be attributed to the variations in the promoter region and this aspect has been reported recently. The observations in the recent reports on the influence of promoter region variants on the metabolism of CYP2C19 substrates might also have been influenced by the copy number variations of CYP2C19. In this paper, we describe copy number variations of CYP2C19 using real-time polymerase chain reaction by comparative Ct method. No copy number variations were observed in the south Indian population indicating the observed discrepancies in genotype-phenotype association studies might be due to the regulatory region polymorphisms as reported earlier.

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Akram, Nabila, Ghulam Mustafa, Anum A. Hanif, Shahzad Tawwab, Shabbir Hussain, Haiba Kaul und Shahida Mohsin. „Cytochrome 2C19 and paraoxonase-1 polymorphisms and clopidogrel resistance in ischemic heart disease patients“. Personalized Medicine 16, Nr. 5 (September 2019): 379–86. http://dx.doi.org/10.2217/pme-2018-0030.

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Aim: Polymorphisms in cytochrome P450 (CYP) 2C19 and paraoxonase-1 (PON-1) genes are thought to be involved in clopidogrel high on treatment reactivity in ischemic heart disease (IHD) patients. Methods: A total of 240 patients with IHD were screened for CYP2C19 loss-of-function alleles (LOF; *2, *3) and PON-1 Q192R. Patients were classified as responders and nonresponders to clopidogrel based upon platelet aggregation studies. Genotyping of the CYP2C19 and PON-1 allele was carried out by PCR-RFLP. Results: Results showed that 14.3% of the patients were nonresponders, whereas 85.7% were responders to the clopidogrel therapy. CYP2C19*3 allele showed significant association with clopidogrel high on treatment reactivity in IHD patients. Conclusion: Result of our study demonstrate that IHD patients with CYP2C19*3 allele can face the problem of clopidogrel high on treatment reactivity in Punjabi Pakistani population.

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Olie, Renske H., Rachelle R. K. Hensgens, Petal A. H. M. Wijnen, Leo F. Veenstra, Bianca T. A. de Greef, Minka J. A. Vries, Paola E. J. van der Meijden et al. „Differential Impact of Cytochrome 2C19 Allelic Variants on Three Different Platelet Function Tests in Clopidogrel-Treated Patients“. Journal of Clinical Medicine 10, Nr. 17 (03.09.2021): 3992. http://dx.doi.org/10.3390/jcm10173992.

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On-treatment platelet reactivity in clopidogrel-treated patients can be measured with several platelet function tests (PFTs). However, the agreement between different PFTs is only slight to moderate. Polymorphisms of the CYP2C19 gene have an impact on the metabolization of clopidogrel and, thereby, have an impact on on-treatment platelet reactivity. The aim of the current study is to evaluate the differential effects of the CYP2C19 genotype on three different PFTs. Methods: From a prospective cohort study, we included patients treated with clopidogrel following percutaneous coronary intervention (PCI). One month after PCI, we simultaneously performed three different PFTs; light transmission aggregometry (LTA), VerifyNow P2Y12, and Multiplate. In whole EDTA blood, genotyping of the CYP2C19 polymorphisms was performed. Results: We included 308 patients treated with clopidogrel in combination with aspirin (69.5%) and/or anticoagulants (33.8%) and, based on CYP2C19 genotyping, classified them as either extensive (36.4%), rapid (34.7%), intermediate (26.0%), or poor metabolizers (2.9%). On-treatment platelet reactivity as measured by LTA and VerifyNow is significantly affected by CYP2C19 metabolizer status (p < 0.01); as metabolizer status changes from rapid, via extensive and intermediate, to poor, the mean platelet reactivity increases accordingly (p < 0.01). On the contrary, for Multiplate, no such ordering of metabolizer groups was found (p = 0.10). Conclusions: For VerifyNow and LTA, the on-treatment platelet reactivity in clopidogrel-treated patients correlates well with the underlying CYP2C19 polymorphism. For Multiplate, no major effect of genetic background could be shown, and effects of other (patient-related) variables prevail. Thus, besides differences in test principles and the influence of patient-related factors, the disagreement between PFTs is partly explained by differential effects of the CYP2C19 genotype.

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Bai, Yunxue, Ruicheng Huang, Lagen Wan und Rui Zhao. „Association between CYP2C19 gene polymorphisms and lipid metabolism in Chinese patients with ischemic stroke“. Journal of International Medical Research 48, Nr. 7 (Juli 2020): 030006052093465. http://dx.doi.org/10.1177/0300060520934657.

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Objective The CYP2C19 genetic variation may be involved in the development of atherosclerotic cardiovascular disease (ASCVD). Serum lipid levels are important risk factors for ASCVD, but the effect of the CYP2C19 gene on serum lipid metabolism remains unclear. This retrospective cohort study investigated the relationship between the CYP2C19 gene polymorphism and serum lipid levels in patients with ischemic stroke (IS). Methods IS patients (n = 230) and control subjects (n = 100) were enrolled. All patients were diagnosed with IS via clinical manifestations and brain magnetic resonance imaging. All patients were genotyped. Results Triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and apolipoprotein B (ApoB) levels were significantly higher and high-density lipoprotein-cholesterol (HDL-c) and apolipoprotein A1 (ApoA1) levels were significantly lower in the IS group compared with the control group. Lower ApoA1 levels and higher ApoB levels were significant predictive factors for IS. Patients with higher ApoB levels had a higher risk of IS recurrence. Compared with extensive metabolizers, intermediate and poor CYP2C19 metabolizers had a higher risk of IS recurrence. Conclusions Our study indicates CYP2C19 gene polymorphisms are related to lipid metabolism in patients with IS. IS patients who are poor CYP2C19 metabolizers may have a higher risk of disease recurrence.

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Freynhofer, Matthias, Jolanta Siller-Matula, Karsten Schrör, Kurt Huber und Liana Yukhanyan. „Genetic variability in response to clopidogrel therapy and its clinical implications“. Thrombosis and Haemostasis 105, S 06 (2011): S55—S59. http://dx.doi.org/10.1160/ths10-11-0747.

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SummaryThis article concentrates on individual genetic differences responsible for variations of action of clopidogrel, which have been found to be partially responsible for increased cardiovascular events in patients with coronary artery disease under dual antiplatelet therapy. According to these results, genotyping for the relevant gene polymorphisms, especially for the CYP2C19 loss-of-function alleles, has been discussed to be an effective method of individualising and optimising clopidogrel treatment. However, due to the facts that 1) there are no prospective studies demonstrating a clinical benefit of personalising antiplatelet therapy based on genotyping; 2) CYP2C19 polymorphisms account for only approximately 12% of variability in clopidogrel platelet response; 3) the positive predictive value of CYP2C19 loss-of-function polymorphisms for cardiovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention is only approximately 12% – 20%; 4) it is likely that other clinical factors and risk constellations might be of greater clinical importance; and 5) it is unknown whether a specific genetic polymorphism is capable of influencing outcome for the individual patient; genetic profiling cannot be recommended for routine use at present but will remain of considerable scientific interest.

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Kim, Yun, Su-jin Rhee, Wan Beom Park, Kyung-Sang Yu, In-Jin Jang und SeungHwan Lee. „A Personalized CYP2C19 Phenotype-Guided Dosing Regimen of Voriconazole Using a Population Pharmacokinetic Analysis“. Journal of Clinical Medicine 8, Nr. 2 (10.02.2019): 227. http://dx.doi.org/10.3390/jcm8020227.

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Highly variable and non-linear pharmacokinetics of voriconazole are mainly caused by CYP2C19 polymorphisms. This study aimed to develop a mechanistic population pharmacokinetic model including the CYP2C19 phenotype, and to assess the appropriateness of various dosing regimens based on the therapeutic target. A total of 1,828 concentrations from 193 subjects were included in the population pharmacokinetic analysis. A three-compartment model with an inhibition compartment appropriately described the voriconazole pharmacokinetics reflecting auto-inhibition. Voriconazole clearance in the CYP2C19 intermediate metabolizers (IMs) and poor metabolizers (PMs) decreased by 17% and 53% compared to that in the extensive metabolizers (EMs). There was a time-dependent inhibition of clearance to 16.2% of its original value in the CYP2C19 EMs, and the extent of inhibition differed according to the CYP2C19 phenotypes. The proposed CYP2C19 phenotype-guided initial dosing regimens are 400 mg twice daily (bid) for EMs, 200 mg bid for IMs, and 100 mg bid for PMs. This CYP2C19 phenotype-guided initial dosing regimen will provide a rationale for individualizing the optimal voriconazole therapy.

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Mirzaev, Karin, Sherzod Abdullaev, Kristina Akmalova, Jeannette Sozaeva, Elena Grishina, Gregory Shuev, Laura Bolieva et al. „Interethnic differences in the prevalence of main cardiovascular pharmacogenetic biomarkers“. Pharmacogenomics 21, Nr. 10 (Juli 2020): 677–94. http://dx.doi.org/10.2217/pgs-2020-0005.

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Background: The aim of this study was to determine the prevalence of CYP2C9, VKORC1, CYP2C19, ABCB1, CYP2D6 and SLCO1B1 genes polymorphisms among residents of the Volga region (Chuvash and Mari) and northern Caucasus (Kabardins and Ossetians). Materials & methods: The study involved 845 apparently healthy volunteers of both sexes of the four different ethnic groups living in the Russian Federation: 238 from the Chuvash ethnic group, 206 Mari, 157 Kabardins and 244 Ossetians. Results: Significant differences were identified in allele frequency of CYP2C9, VKORC1, CYP2C19, ABCB1, CYP2D6 and SLCO1B1 genes polymorphisms between the Chuvash and Kabardins, Chuvash and Ossetians, Mari and Kabardians, Mari and Ossetians.

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Muslimova, E. F., S. A. Afanasiev, T. Yu Rebrova, T. N. Sergienko und A. N. Repin. „Association of ITGB3, P2RY12, and CYP2C19 gene polymorphisms with platelet functional activity in patients with coronary heart disease during dual antiplatelet therapy“. Terapevticheskii arkhiv 89, Nr. 5 (15.05.2017): 74–78. http://dx.doi.org/10.17116/terarkh201789574-78.

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Aim. To assess the association of CYP2C19 G681A, P2RY12 H1/H2, and ITGB3 T1565C polymorphisms with the extent of platelet aggregation in patients with coronary heart disease (CHD) during antiplatelet therapy. Subjects and methods. 166 male patients with CHD, living in the Western Siberian Region, were examined. All the patients underwent a test for platelet aggregation induced by ADP (2.5 and 5.0 µm) and epinephrine (0.2 µm). Genotyping was performed using an allele-specific polymerase chain reaction technique. Results. The polymorphic variants of the P2RY12 and ITGB3 genes were ascertained to have no impact on the extent of platelet aggregation in patients receiving clopidogrel and acetylsalicylic acid. An association was found between CYP2C19 681A allele carriage and the increased extent of platelet aggregation induced by ADP. Conclusion. The carriage of the cytochrome P450 CYP2C19 681A allele rather than platelet receptor gene polymorphisms determines a risk for clopidogrel resistance in patients with CHD.

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Ellithi, Moataz, Jordan Baye und Russell A. Wilke. „CYP2C19 genotype-guided antiplatelet therapy: promises and pitfalls“. Pharmacogenomics 21, Nr. 12 (August 2020): 889–97. http://dx.doi.org/10.2217/pgs-2020-0046.

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Pharmacogenetic variants can alter the mechanism of action (pharmacodynamic gene variants) or kinetic processes such as absorption, distribution, metabolism and elimination (pharmacokinetic gene variants). Many initial successes in precision medicine occurred in the context of genes encoding the cytochromes P450 (CYP enzymes). CYP2C19 activates the antiplatelet drug clopidogrel, and polymorphisms in the CYP2C19 gene are known to alter the outcome for patients taking clopidogrel in the context of cardiovascular disease. CYP2C19 loss-of-function alleles are specifically associated with increased risk for coronary stent thrombosis and major adverse cardiovascular events in patients taking clopidogrel following percutaneous coronary intervention. We explore successes and challenges encountered as the clinical and scientific communities advance CYP2C19 genotyping in the context of routine patient care.

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Çayan, Filiz, Lokman Ayaz, Meral Aban, Saffet Dilek und Lülüfer Tamer Gümüş. „Role of CYP2C19 polymorphisms in patients with endometriosis“. Gynecological Endocrinology 25, Nr. 8 (Januar 2009): 530–35. http://dx.doi.org/10.1080/09513590902972059.

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Choi, Chang-Ik, Jung-Woo Bae, Yun-Jeong Lee, Hye-In Lee, Choon-Gon Jang und Seok-Yong Lee. „Effects of CYP2C19 Genetic Polymorphisms on Atomoxetine Pharmacokinetics“. Journal of Clinical Psychopharmacology 34, Nr. 1 (Februar 2014): 139–42. http://dx.doi.org/10.1097/jcp.0b013e3182a608a2.

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Djaffar Jureidini, Isabelle, Nabil Chamseddine, Sose Keleshian, Rania Naoufal, Laila Zahed und Noha Hakime. „Prevalence of CYP2C19 polymorphisms in the Lebanese population“. Molecular Biology Reports 38, Nr. 8 (05.03.2011): 5449–52. http://dx.doi.org/10.1007/s11033-011-0700-y.

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Miftahussurur, Muhammad, Dalla Doohan, Ari Fahrial Syam, Iswan Abbas Nusi, Phawinee Subsomwong, Langgeng Agung Waskito, Hasan Maulahela et al. „CYP2C19 Polymorphisms in Indonesia: Comparison among Ethnicities and the Association with Clinical Outcomes“. Biology 10, Nr. 4 (06.04.2021): 300. http://dx.doi.org/10.3390/biology10040300.

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CYP2C19 polymorphisms are important factors for proton pump inhibitor-based therapy. We examined the CYP2C19 genotypes and analyzed the distribution among ethnicities and clinical outcomes in Indonesia. We employed the polymerase chain reaction-restriction fragment length polymorphism method to determine the CYP2C19 genotypes and evaluated inflammation severity with the updated Sydney system. For CYP2C19*2, 46.4% were the homozygous wild-type allele, 14.5% were the homozygous mutated allele, and 39.2% were the heterozygous allele. For CYP2C19*3, 88.6% were the homozygous wild-type allele, 2.4% were the homozygous mutated allele, and 9.0% were the heterozygous allele. Overall, the prevalence of rapid, intermediate, and poor metabolizers in Indonesia was 38.5, 41.6, and 19.9%, respectively. In the poor metabolizer group, the frequency of allele *2 (78.8%) was higher than the frequency of allele *3 (21.2%). The Papuan had a significantly higher likelihood of possessing poor metabolizers than the Balinese (OR 11.0; P = 0.002). The prevalence of poor metabolizers was lower compared with the rapid and intermediate metabolizers among patients with gastritis and gastroesophageal reflux disease. Intermediate metabolizers had the highest prevalence, followed by rapid metabolizers and poor metabolizers. Dosage adjustment should therefore be considered when administering proton pump inhibitor-based therapy in Indonesia.

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Солодун und M. Solodun. „Genetic markers 1-year outcome of myocardial infarction with St-segment elevation“. Journal of New Medical Technologies. eJournal 10, Nr. 1 (19.05.2016): 0. http://dx.doi.org/10.12737/18640.

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Aim: to analyze the prognostic value of gene polymorphisms ACE (D/I), SLCO1B1 (Val174Ala), LIPC (C514T), CYP2C19*2, CYP2C19*3, ADRB1 (Ser49Gly), ADRB1 (Arg389Gly) of patients with ST-segment elevation myocardial infarction (STEMI). Materials and methods: 145 patients with STEMI from 45 to 75 years of age were involved into the study. All patients were prescribed all recommended preparations improving prognosis (statins, angiotensin-converting enzyme inhibitors, beta-blockers, clopidogrel as part of dual antiplatelet therapy) from the first day of hospitalization. To determine gene polimorphismspolimerase chain reactionwas used. Prognosis was assessed by a combined endpoint, including cardiovascular mortality, nonfatal myocardial infarction, unplanned revascularization of coronary arteries and hospitalization for unstable angina, throughout 12 months. Results. The II genotype of the polymorphic gene ACE (I / D) is a predictor of the 12-month STEMI fa-vorable outcome. Allele Ser of the polymorphic gene ADRB1 Ser49Gly is associated with an increased incidence of adverse cardiovascular events within 12 months after STEMI. Gene polymorphisms SLCO1B1 (Val174Ala), CYP2C19*2, CYP2C19*3, ADRB1 (Arg389Gly), LIPC (C514T) does not affect the 12-month forecast after STEMI. Conclusions. Genotyping of ACE (I /D) and ADRB1 Ser49Gly can be used to assess the long-term prog-nosis and effectiveness of pharmacotherapy STEMI by means of personalizing it.

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Lyerly, Michael J., Kelly Bartlett und Karen C. Albright. „Role of CYP2C19 alleles in the management of recurrent ischemic stroke“. Neurology: Clinical Practice 9, Nr. 2 (21.12.2018): 140–44. http://dx.doi.org/10.1212/cpj.0000000000000584.

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Purpose of reviewCYP2C19 is the primary enzyme involved in the activation of clopidogrel, an antiplatelet agent used for secondary stroke prevention. An individual's CYP2C19 alleles are used to understand their CYP2C19-clopidogrel metabolizer phenotype. Single nucleotide polymorphisms of the CYP2C19 gene result in altered metabolism of this prodrug.Recent findingsThree ischemic stroke cases were treated with clopidogrel. Despite confirming adequate drug exposure, medication adherence, and ruling out drug-drug interactions, all had recurrent ischemic stroke. Each case had a CYP2C19 *2/*17 genotype, categorizing them as intermediate clopidogrel metabolizers. Even with the gain-of-function allele, the loss-of-function allele resulted in lack of prodrug activation, leading to decreased efficacy in platelet inhibition.SummaryThese cases illustrate the importance of a thoughtful approach to secondary stroke prevention and demonstrate the utility of pharmacogenomic testing in clopidogrel hyporesponders. Recognition of the importance of CYP2C19 genotyping has the potential to enable better selection of appropriate secondary prevention strategies.

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Hoh, Brian L., Yan Gong, Caitrin W. McDonough, Michael F. Waters, Adrienne J. Royster, Tiffany O. Sheehan, Ben Burkley et al. „CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease“. Journal of Neurosurgery 124, Nr. 6 (Juni 2016): 1746–51. http://dx.doi.org/10.3171/2015.6.jns15795.

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OBJECT Symptomatic intracranial atherosclerotic disease (ICAD) has a high risk of recurrent stroke. Genetic polymorphisms in CYP2C19 and CES1 are associated with adverse outcomes in cardiovascular patients, but have not been studied in ICAD. The authors studied CYP2C19 and CES1 single-nucleotide polymorphisms (SNPs) in symptomatic ICAD patients. METHODS Genotype testing for CYP2C19*2, *3, *8, *17 and CES1 G143E was performed on 188 adult symptomatic ICAD patients from 3 medical centers who were medically managed with clopidogrel and aspirin. Testing was performed prospectively at 1 center, and retrospectively from a DNA sample biorepository at 2 centers. Multiple logistic regression and Cox regression analysis were performed to assess the association of these SNPs with the primary endpoint, which was a composite of transient ischemic attack (TIA), stroke, myocardial infarction, or death within 12 months. RESULTS The primary endpoint occurred in 14.9% of the 188 cases. In multiple logistic regression analysis, the presence of the CYP2C19 loss of function (LOF) alleles *2, *3, and *8 in the medically managed patients was associated with lower odds of primary endpoint compared with wild-type homozygotes (odds ratio [OR] 0.13, 95% CI 0.03–0.62, p = 0.0101). Cox regression analysis demonstrated the CYP2C19 LOF carriers had a lower risk for the primary endpoint, with hazard ratio (HR) of 0.27 (95% CI 0.08–0.95), p = 0.041. A sensitivity analysis of a secondary composite endpoint of TIA, stroke, or death demonstrated a significant trend in multiple logistic regression analysis of CYP2C19 variants, with lower odds of secondary endpoint in patients carrying at least 1 LOF allele (*2, *3, *8) than in wild-type homozygotes (OR 0.27, 95% CI 0.06–1.16, p = 0.078). Cox regression analysis demonstrated that the carriers of CYP2C19 LOF alleles had a lower risk forthe secondary composite endpoint (HR 0.22, 95% CI 0.05–1.04, p = 0.056). CONCLUSIONS This is the first study examining genetic variants and their effects in symptomatic ICAD. Variant alleles of CYP2C19 (*2, *3, *8) were associated with lower odds of the primary and secondary composite endpoints. However, the direction of the association was opposite of what is expected based on this SNP. This may reflect an incomplete understanding of this genetic variation and its effect in symptomatic ICAD and warrants further investigations.

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Pan, Yuesong, Runqi Wangqin, Hao Li, Yilong Wang, Xia Meng, S. Claiborne Johnston, Tabassome Simon et al. „F2R Polymorphisms and Clopidogrel Efficacy and Safety in Patients With Minor Stroke or TIA“. Neurology 96, Nr. 1 (22.10.2020): e1-e9. http://dx.doi.org/10.1212/wnl.0000000000011078.

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ObjectiveTo investigate the association between protease-activated receptor-1 (PAR-1) gene F2R polymorphisms and efficacy of clopidogrel for minor stroke or TIA.MethodsThree single nucleotide polymorphisms (CYP2C19*2 [681G>A, rs4244285], CYP2C19*3 [636G>A, rs4986893], and F2R [IVSn-14 A/T, rs168753]) were genotyped among 2,924 patients randomized to clopidogrel plus aspirin (n = 1,461) or aspirin alone (n = 1,463). The primary efficacy outcome was new stroke (ischemic or hemorrhagic) and the safety outcome was any bleeding.ResultsOverall, 859 (29.4%) were AA homozygotes, 1,479 (50.6%) were AT heterozygotes, and 586 (20.0%) were TT homozygotes for F2R IVSn-14 polymorphisms; 1,716 (58.7%) were carriers of at least 1 CYP2C19 loss-of-function allele (*2 or *3). Compared with aspirin alone, patients with clopidogrel–aspirin treatment had a low risk of new stroke in patients with AT genotype (7.6% vs 11.3%; hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44–0.89) and TT genotype (5.8% vs 11.6%; HR, 0.46; 95% CI, 0.25–0.82) but not in carriers of the AA genotype (10.8% vs 11.6%; HR, 0.95; 95% CI, 0.63–1.44) (p = 0.03 for interaction). The association between F2R IVSn-14 A/T polymorphism and clopidogrel response was present regardless of the carrier status of the CYP2C19 loss-of-function alleles. The F2R IVSn-14 genotypes were not associated with the risk of any bleeding for clopidogrel–aspirin treatment (p = 0.66 for interaction).ConclusionsAmong patients with minor ischemic stroke or TIA who were receiving clopidogrel and aspirin, those carrying the F2R IVSn-14 T allele had a lower rate of recurrent stroke than those who were not.Clinicaltrials.gov IdentifierNCT00979589.

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Kovacheva, Katya S., Petya A. Nikolova, Valentin V. Hristov, Diana I. Pendicheva, Sotir T. Marchev, Tihomir R. Rashev, Georgi M. Golemanov, Zornica B. Kamburova, Maria N. Simeonova und Rusi G. Marev. „Preliminary Data from a Study on Polymorphism RS4244285 of P4502c19 Cytochrome Gene in Patients with Acute Coronary Syndrome, Undergoing Treatment with Dual Antiplatelet Therapy With Clopidogrel and Aspirin“. Journal of Biomedical and Clinical Research 9, Nr. 1 (01.09.2016): 65–71. http://dx.doi.org/10.1515/jbcr-2016-0010.

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Summary Administration of antiplatelet therapy Aspirin and Clopidogrel (CLP) is a corner stone inpatients with Acute Coronary Syndrome (ACS) undergoing Percutaneous Coronary Intervention (PCI) with/without stent implantation. The CYP2C19*2 allele is the most important genetic variant determining response to CLP. We aim to investigate frequency of CYP2C19*2 polymorphism in patients with ACS and significance for the individual response to CLP therapy. The preliminary data of a study including a total of 120 patients with ACS undergoing PCI with stent placement and treated with dual antiplatelet therapy (CLP and Aspirin) are presented. So far 18 patients (41-81 year age) are tested for CYP2C19*l/*2 polymorphisms. The genotype CYP2C19*1/*1; CYP2C19*l/*2 and CYP2C19*2/*2 is demonstrated in 50%, 33%, 17% respectively, of the patients. The established frequency of CYP2C 19*2 allele (33%) is significantly higher (x2=5.220; p=0.022) than in healthy Bulgarian individuals (16%). In-stent thrombosis have developed 3 (17%) of patients: 2 are C YP2C19* l/*2 carriers, and 1 - homozygous CYP2C19*2/*2. The preliminary data demonstrate high prevalence of CYP2C19*2 polymorphism in patients with ACS and point to significance of the variant for CLP therapy. Further extension of the study with larger samples and monitoring of the patients are required to determine the effects of the polymorphism on the prognosis for major adverse cardiovascular events.

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Garcia, Sofia, Michael Schuh, Anvir Cheema, Herjot Atwal und Paldeep S. Atwal. „Palpitations and Asthenia Associated with Venlafaxine in a CYP2D6 Poor Metabolizer and CYP2C19 Intermediate Metabolizer“. Case Reports in Genetics 2017 (2017): 1–4. http://dx.doi.org/10.1155/2017/6236714.

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Cardiotoxicity has been extensively reported in venlafaxine (VEN) overdoses. Asthenia is also among the common side effects described for this antidepressant. VEN is metabolized mainly by CYP2D6 and to a minor extent by CYP2C19 to the major active metabolite O-desmethylvenlafaxine (ODV). Altered pharmacokinetic parameters in patients with polymorphisms in the CYP2D6 and CYP2C19 genes that result in decreased enzymatic activity have been documented. Here we describe a patient case of VEN associated palpitations and asthenia. The patient takes VEN extended release 150 mg twice daily. Genotyping confirmed the patient is a poor metabolizer for CYP2D6 and an intermediate metabolizer for CYP2C19. We propose that the palpitations and asthenia are related to sustained VEN exposure due to reduced metabolism.

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Melin, Kyle, Jorge Duconge und Dagmar F. Hernandez Suarez. „2220“. Journal of Clinical and Translational Science 1, S1 (September 2017): 25. http://dx.doi.org/10.1017/cts.2017.99.

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OBJECTIVES/SPECIFIC AIMS: The objective of this study is to measure the association of CYP2C19 (*1-*8,*17), ABCB1(C3435T; rs1045642), PON1 (p.Q192R; rs662), and B4GALT2 (c.909 C>T and c.366 G>C) gene polymorphisms in the Caribbean Hispanic population with major adverse cardiovascular events (MACE). METHODS/STUDY POPULATION: Patients of Caribbean Hispanic ethnicity from all geographic regions of the Island of Puerto Rico, male and female, aged >21 will be recruited. Cases will consist of patients receiving a daily clopidogrel dose of 75 mg following acute coronary syndrome (ACS) who experience a MACE within the first year of treatment. Control study patients must have received clopidogrel 75 mg daily for a minimum of 1 year without experiencing MACE. Genomic DNA samples will be genotyped to determine the frequency distribution of major CYP2C19, ABCB1, PON1, and B4GALT2 gene polymorphisms. Observed frequencies will be compared with other reported populations. An association study will be performed between genetic variables and MACE and a multivariable logistic regression model (additive) will be constructed. RESULTS/ANTICIPATED RESULTS: We anticipate finding a significant association between major genetic determinants of clopidogrel response and MACE where cases with MACE will carry higher frequency of CYP2C19, ABCB1, PON1, and B4GALT2. DISCUSSION/SIGNIFICANCE OF IMPACT: As the range of multiloci allelic combinations in admixed Caribbean Hispanics is higher than in other populations due to its unique 500-year history of genomic admixture, a wide spectrum of genetic variances is expected to be present in the study population. Determining the prevalence and effect of CYP2C19, ABCB1, PON1, and B4GALT2 polymorphisms holds the potential to personalize anti-platelet treatment for Caribbean Hispanic patients requiring treatment after ACS.

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Akasaka, Tomonori, Daisuke Sueta, Yuichiro Arima, Noriaki Tabata, Seiji Takashio, Yasuhiro Izumiya, Eiichiro Yamamoto et al. „Association of CYP2C19 variants and epoxyeicosatrienoic acids on patients with microvascular angina“. American Journal of Physiology-Heart and Circulatory Physiology 311, Nr. 6 (01.12.2016): H1409—H1415. http://dx.doi.org/10.1152/ajpheart.00473.2016.

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Categorization as a cytochrome P450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by CYP2C19 epoxygenases and anti-inflammatory properties, especially in microvascular tissues. We examined the association of CYP2C19 polymorphisms and EETs on microvascular angina (MVA) caused by coronary microvascular dysfunction. We examined CYP2C19 genotypes in patients with MVA ( n = 71) and healthy subjects as control ( n = 71). MVA was defined as the absence of coronary artery stenosis and epicardial spasms and the presence of inversion of lactic acid levels between intracoronary and coronary sinuses in acetylcholine-provocation test or the adenosine-triphosphate-induced coronary flow reserve ratio was below 2.5. CYP2C19 PM have two loss-of-functon alleles (*2, *3). We measured serum dihydroxyeicosatrienoic acid (DHET) as representative EET metabolite. MVA group showed significantly higher CYP2C19 PM incidence (35% vs. 16%; P = 0.007) and high sense C-reactive protein (hs-CRP) levels (0.127 ± 0.142 vs. 0.086 ± 0.097 mg/dl; P = 0.043) than those of controls. Moreover, in MVA group, hs-CRP levels in CYP2C19 PM were significantly higher than that of non-PM (0.180 ± 0.107 vs. 0.106 ± 0.149 mg/dl, P = 0.045). Multivariate analysis indicated that smoking, hypertension, high hs-CRP, and CYP2C19 PM are predictive factors for MVA. In MVA group, DHET levels for CYP2C19 PM were significantly lower than that of non-PM [10.9 ± 1.64 vs. 14.2 ± 5.39 ng/ml, P = 0.019 (11,12-DHET); 15.2 ± 4.39 vs. 17.9 ± 4.73 ng/ml, P = 0.025 (14,15-DHET)]. CYP2C19 variants are associated with MVA. The decline of EET-based defensive mechanisms owing to CYP2C19 variants may affect coronary microvascular dysfunction.

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Bhat, Dr Sabreen Bashir, und Poornima R. „PHARMACOGENETIC VARIATIONS RELATED TO CLOPIDOGREL RESISTANCE AND ITS CLINICAL IMPLICATIONS: AN ISSUE WHICH REMAINS LARGELY UNADDRESSED“. Asian Journal of Pharmaceutical and Clinical Research 9, Nr. 5 (01.09.2016): 194. http://dx.doi.org/10.22159/ajpcr.2016.v9i5.13210.

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ABSTRACTObjectives: Antiplatelet therapy with either clopidogrel alone or in combination with aspirin is the mainstay prophylactic drug therapy followingpercutaneous coronary intervention and long-term prevention of cardiovascular and cerebrovascular events. Non-responders/semi-responders toclopidogrel are reported to have increased incidences of adverse outcomes like recurrent ischemic attacks. Variability in response to clopidogrel ismore common among Asians, and it is as high as 70% in some of the Asian communities. Researchers attribute inter-individual variations in responseto clopidogrel to various pharmacogenetic determinants. Polymorphisms of multidrug resistance protein 1, CYP2C19 and its alleles, P2Yadenosine diphosphate (ADP) receptor are concluded to be specific to clopidogrel resistance in Indian population.Methods: A thorough literature search was done use different keywords such as clopidogrel resistance, pharmacogenomics, pharmacogeneticvariability, and ethnic variability from database sources such as Google Scholar, Medline, PubMed Central, and Scopus.Results and Conclusion: Literature revealed a disparity between various pharmacogenetic determinants of clopidogrel resistance, particularly inthe Asian population. Few studies suggest that there is no significant association between clopidogrel response variability and ADP receptor P2Yand P2Y gene polymorphisms. Variation in the cytochrome P450 2C19 (CYP2C19) gene coding for the CYP2C19 enzyme, involved in metabolismand conversion of the clopidogrel to active metabolites is considered one of the major determinants of clopidogrel resistance in some populations.Pooled data from various studies suggest that variability in clopidogrel response cannot be attributed to a single gene polymorphism and is thoughtto be multifactorial. However, disparity in the data related to the specific gene polymorphisms responsible for the encountered clopidogrel resistancenecessitates the further evaluation of genome.12Keywords: Clopidogrel, Clopidogrel resistance, Single gene polymorphisms, Inter-individual variability.1, and P2Y121

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Bozdag, Gurkan, Alpaslan Alp, Zeynep Saribas, Selcuk Tuncer, Tarik Aksu und Timur Gurgan. „CYP17 and CYP2C19 gene polymorphisms in patients with endometriosis“. Reproductive BioMedicine Online 20, Nr. 2 (Februar 2010): 286–90. http://dx.doi.org/10.1016/j.rbmo.2009.11.007.

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Luo, Huai-Rong, Vasileios Aloumanis, Keh-Ming Lin, David Gurwitz und Yu-Jui Yvonne Wan. „Polymorphisms of CYP2C19 and CYP2D6 in Israeli Ethnic Groups“. American Journal of PharmacoGenomics 4, Nr. 6 (2004): 395–401. http://dx.doi.org/10.2165/00129785-200404060-00006.

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Tamer, L., B. Ercan, S. Ercan, N. Ates, C. Ates, K. Öcal, M. Dirlik, S. Aydin und U. Atik. „CYP2C19 Polymorphisms in Patients with Gastric and Colorectal Carcinoma“. International Journal of Gastrointestinal Cancer 37, Nr. 1 (2006): 1–6. http://dx.doi.org/10.1385/ijgc:37:1:1.

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Spigset, O., K. Granberg, S. Hägg, Å. Norström und R. Dahlqvist. „Relationship between fluvoxamine pharmacokinetics and CYP2D6/CYP2C19 phenotype polymorphisms“. European Journal of Clinical Pharmacology 52, Nr. 2 (29.04.1997): 129–33. http://dx.doi.org/10.1007/s002280050261.

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Suzuki, Yoshiharu, Takuya Yoshihashi, Kazuhiro Takahashi, Kinji Furuya, Nobuhiro Ohkohchi, Tatsuya Oda und Masato Homma. „Drug–Drug Interaction between Tacrolimus and Vonoprazan in Kidney Transplant Recipients“. Journal of Clinical Medicine 10, Nr. 17 (31.08.2021): 3964. http://dx.doi.org/10.3390/jcm10173964.

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Kidney transplant recipients with tacrolimus-based immunosuppressive therapy are often treated with proton-pump inhibitors (PPIs) to prevent gastric ulcer complications. Vonoprazan, a potassium-competitive acid blocker, is a novel PPI possessing different metabolic pathways from conventional PPIs (e.g., omeprazole, lansoprazole and rabeprazole). However, no data are available on the change in blood concentration of tacrolimus after switching rabeprazole, a conventional PPI, to vonoprazan coadministration in the initial period of post-transplantation. This is a retrospective study of 18 kidney transplant recipients. The blood concentration and the concentration to dose (C/D) ratio of tacrolimus were compared before and after switching from rabeprazole to vonoprazan. Impacts of CYP2C19 and CYP3A5 genetic polymorphisms on the drug–drug interaction were also examined. The median (range) trough concentration of tacrolimus was significantly increased from 5.2 (3.6–7.4) to 8.1 (6.1–11.7) ng/mL (p < 0.0005) after switching from rabeprazole to vonoprazan. The C/D ratio of tacrolimus was also significantly increased from 38.1 (16.5–138.1) to 48.9 (26.2–207.2) (p < 0.0005). The percent changes of tacrolimus concentrations and C/D were 65.8% and 41.8%, respectively. CYP2C19 and CYP3A5 genetic polymorphisms did not affect the change in concentration and C/D ratio of tacrolimus. The present study indicates that vonoprazan coadministration increases the tacrolimus concentration regardless of CYP2C19 or CYP3A5 genetic polymorphisms. Thus, frequent monitoring of blood tacrolimus concentration is required when vonoprazan is introduced as an intensive gastric acid blocker in the early phase of post-transplantation.

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Kanjanasilp, Juntip, Ratree Sawangjit, Sirikhwan Phanthaisong und Wongvaruth Borihanthanawuth. „A meta-analysis of effects of CYP2C9 and CYP2C19 polymorphisms on phenytoin pharmacokinetic parameters“. Pharmacogenomics 22, Nr. 10 (Juli 2021): 629–40. http://dx.doi.org/10.2217/pgs-2020-0151.

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Aim: Phenytoin is metabolized through CYP2C9 and CYP2C19 . Polymorphisms of CYP2C9 and CYP2C19 may increase plasma concentration and side effects. Materials & methods: Systematic review and meta-analysis were performed to evaluate the effects of CYP2C9 and CYP2C19 polymorphism on pharmacokinetic parameters. PubMed, Science Direct, Cochrane library, and Thai databases were systematically searched. Results: Eight observational studies, comprising a total of 633 patients were included. Michaelis–Menten constant was significantly higher in the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups as compared with the control groups (CYP2C9EM/CYP2C19EM) at 2.16 and 1.55 mg/l (p < 0.00001, p < 0.0001). The maximum rate of action was significantly lower in the control groups as compared with the polymorphism of CYP2C9IM/CYP2C19EM and CYP2C9IM/CYP2C19IM groups at 3.10 and 3.53 mg/kg/day (p = 0.00001, <0.0001). Conclusion: The dosage regimen for patients in the CYP2C9IM group to achieve phenytoin therapeutic levels was 2.1–3.4 mg/kg/day.

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Yu, Ya-Yen, Shih-Ming Tsao, Wen-Ta Yang, Wei-Chang Huang, Ching-Hsiung Lin, Wei-Wen Chen, Shun-Fa Yang, Hui-Ling Chiou und Yi-Wen Huang. „Association of Drug Metabolic Enzyme Genetic Polymorphisms and Adverse Drug Reactions in Patients Receiving Rifapentine and Isoniazid Therapy for Latent Tuberculosis“. International Journal of Environmental Research and Public Health 17, Nr. 1 (27.12.2019): 210. http://dx.doi.org/10.3390/ijerph17010210.

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Weekly rifapentine and isoniazid therapy (3HP) is the most frequent treatment for latent tuberculosis infection (LTBI). However, the association between major adverse drug reactions (ADRs) and drug metabolic enzyme single-nucleotide polymorphisms (SNPs) remains unclear. In this study, 377 participants who received the 3HP regimen were recruited and examined for genotyping of CYP5A6, CYP2B6, CYP2C19, CYP2E1, and NAT2 SNPs. In our study, 184 participants (48.4%) developed ADRs. Moreover, CYP2C19 rs4986893 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 2.231 [1.015–4.906]), CYP2E1 rs2070676 (CC vs. CG+GG, OR [95% CI]: 1.563 [1.022–2.389]), and CYP2E1 rs2515641 (CC vs. CT+TT, OR [95% CI]: 1.903 [1.250–2.898]) were associated with ADR development. In conclusion, CYP2C19 and CYP2E1 SNPs may provide useful information regarding ADRs in LTBI patients receiving the 3HP regimen.

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Rodrigues-Silva, Christielly, Agostinho Tavares Semedo, Hiasmin Franciely da Silva Neri, Rosana Pereira Vianello, Carlos Galaviz-Hernández, Martha Sosa-Macías, Rodrigo Bernini de Brito und Paulo César Ghedini. „The CYP2C19*2 and CYP2C19*17 Polymorphisms Influence Responses to Clozapine for the Treatment of Schizophrenia“. Neuropsychiatric Disease and Treatment Volume 16 (Februar 2020): 427–32. http://dx.doi.org/10.2147/ndt.s228103.

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