Academic literature on the topic 'CYP2C19-polymorphisms'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'CYP2C19-polymorphisms.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "CYP2C19-polymorphisms"
1
Mărginean, Alina, Claudia Bănescu, Valeriu Moldovan, Alina Scridon, Mihai Mărginean, Rodica Bălaşa, Smaranda Maier, Mariana Ţăruşi, and 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, no. 3 (July 9, 2016): 255–65. http://dx.doi.org/10.1177/1076029616629211.
Full textAbstract:
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.
2
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, no. 1 (June 2, 2006): 171–76. http://dx.doi.org/10.1017/s0950268806006613.
Full textAbstract:
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.
3
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, no. 12 (2013): 1223–31. http://dx.doi.org/10.1160/th13-03-0263.
Full textAbstract:
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.
4
Islam, Md Rabiul, Tasnova Tasnim Nova, NAM Momenuzzaman, Sikder Nahidul Islam Rabbi, Ishrat Jahan, Thomas Binder, Mohammad Safiqul Islam, Abul Hasnat, and Zabun Nahar. "Prevalence of CYP2C19 and ITGB3 polymorphisms among Bangladeshi patients who underwent percutaneous coronary intervention." SAGE Open Medicine 9 (January 2021): 205031212110422. http://dx.doi.org/10.1177/20503121211042209.
Full textAbstract:
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.
5
Riaz, Sana, Atika Mansoor, Saima Siddiqi, Muhammad Usman Tareen, Sana Rubab, Ayesha Batool, Anwarullah, and Aneesa Sultan. "Association of CYP2C19*2 and *17 genetic variants with hypertension in Pakistani population." Tropical Journal of Pharmaceutical Research 18, no. 4 (May 24, 2021): 851–55. http://dx.doi.org/10.4314/tjpr.v18i4.24.
Full textAbstract:
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.
6
Tantsura, Lyudmyla, Olena Pylypets, Yevhen Tantsura, and Dmytro Tretiakov. "Possibilities of optimizing approaches to the treatment of resistant epilepsy in children using pharmacogenetic studies data." Ukrains'kyi Visnyk Psykhonevrolohii 27, no. 3 (September 5, 2019): 92–96. http://dx.doi.org/10.36927/2079-0325-v27-is3-2019-18.
Full textAbstract:
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.
7
Arévalo-Galvis, Azucena, William A. Otero-Regino, Gloria N. Ovalle-Celis, Eliana R. Rodríguez-Gómez, and Alba A. Trespalacios-Rangel. "Prevalence of CYP2C19 polymorphism in Bogotá, Colombia: The first report of allele *17." PLOS ONE 16, no. 1 (January 27, 2021): e0245401. http://dx.doi.org/10.1371/journal.pone.0245401.
Full textAbstract:
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.
8
Song, Yan, Miao-xin Jia, Guang Yang, Xin-yuan Feng, Dong-hong Yin, Jian-bang Kang, Qiang Zhao, and Jin-ju Duan. "Association of CYP2C19 and UGT1A4 polymorphisms with voriconazole-induced liver injury." Personalized Medicine 17, no. 1 (January 2020): 15–22. http://dx.doi.org/10.2217/pme-2019-0042.
Full textAbstract:
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.
9
Kim, In-Suk, Young-Hoon Jeong, and 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, no. 11 (November 16, 2008): 982. http://dx.doi.org/10.1182/blood.v112.11.982.982.
Full textAbstract:
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.
10
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, no. 2(75) (2021): 62–69. http://dx.doi.org/10.51922/1818-426x.2021.2.62.
Full textAbstract:
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.
Dissertations / Theses on the topic "CYP2C19-polymorphisms"
1
Semedo, Agostinho Tavares. "Avaliação da influência dos polimorfismos CYP2C19*2 e CYP2C19*17 na resposta ao tratamento à clozapina na esquizofrenia." Universidade Federal de Goiás, 2017. http://repositorio.bc.ufg.br/tede/handle/tede/6899.
Full textAbstract:
Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-06T14:02:56Z
No. of bitstreams: 2
Dissertação - Agostinho Tavares Semedo - 2017.pdf: 2917656 bytes, checksum: 0a4e0b9aac67ef54832262a3818baf13 (MD5)
license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-03-06T14:03:17Z (GMT) No. of bitstreams: 2 Dissertação - Agostinho Tavares Semedo - 2017.pdf: 2917656 bytes, checksum: 0a4e0b9aac67ef54832262a3818baf13 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)
Made available in DSpace on 2017-03-06T14:03:17Z (GMT). No. of bitstreams: 2 Dissertação - Agostinho Tavares Semedo - 2017.pdf: 2917656 bytes, checksum: 0a4e0b9aac67ef54832262a3818baf13 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-02-22
Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Clozapine (CLZ) has been an antipsychotic of choice in treatment refractory schizophrenia (TRS). However, around 30% of the patients do not respond appropriately to this antipsychotic, being in this way, super-refractory schizophrenia (SRS). Genetic polymorphisms from cytochrome P450 enzymes can influence the metabolism of drugs and individual variability therapeutic response. Considering CYP2C19 a polymorphic enzyme with second major participation in the metabolism of CLZ, the aim of the present study was to analyse the influence of CYP2C19*2 and *17 polymorphisms in the response to the treatment to CLZ. The present study included 69 schizophrenic patients and 137 healthy individuals as a control group. Genotyping test and analysis of polymorphisms was done using sequencing technique and enzymatic restriction (RFLP) for patients and control’s group respectively. The results showed a major distribution of CYP2C19*17 polymorphism in patients’s group in comparison to control’s group. The CYP2C19*2 polymorphism was significantly higher in patients with TRS than to patients with SRS. The CYP2C19*17 polymorphism in heterozygous (CYP2C19*1/*17) was associated to higher clozapine’s doses in polytherapy and less efficient therapeutic response in SRS patients’s group, while the CYP2C19*2 was associated to lower clozapine’s doses in monotherapy and good therapeutic response in TRS patients’s group. In addition, parameters like daily mean clozapine dose, symptons severity according to Brief Psyquiatric Rating Scale (BPRS) and female individuals were also associated to super-refractoriness response to CLZ having a major distribution in SRS patients’s group. These findings suggest that new treatment strategies must be evaluated for the patients carriers of CYP2C19*17 polymorphism with SRS, above all the female individuals. Future studies with larger sample should be relevant to give more consistence to these findings.
A clozapina (CLZ) é um antipsicótico de escolha no tratamento de esquizofrenia refratária (ER). No entanto, cerca de 30% dos pacientes não respondem adequadamente à este antipsicótico, sendo considerados super-refratários ao tratamento (ESR). Sabe-se que polimorfismos genéticos nas enzimas do citocromo P450 podem influenciar o metabolismo das drogas, interferindo na variabilidade individual de resposta terapêutica. Sendo a CYP2C19 uma enzima altamente polimórfica e com a segunda maior participação no metabolismo da CLZ, o presente estudo visou analisar as influências dos polimorfismos CYP2C19*2 e *17 na resposta ao tratamento à este antipsicótico. O estudo incluiu 69 pacientes diagnosticados com esquizofrenia e 137 indivíduos saudáveis como controle. Utilizou-se a técnica de sequenciamento na genotipagem dos pacientes e a restrição enzimática (RFLP- Restrition Fragment Length Polymorphism) para o controle. Os resultados mostraram uma maior distribuição do polimorfismo CYP2C19*17 no grupo dos pacientes em comparação ao grupo controle. O polimorfismo CYP2C19*2 teve uma maior distribuição no grupo dos pacientes com ER em comparação aos pacientes com ESR. O polimorfismo CYP2C19*17 em heterozigose (CYP2C19*1/*17) estava associado à maior dose de CLZ em politerapia e resposta terapêutica menos eficiente no grupo dos pacientes com ESR, enquanto que a CYP2C19*2 em heterozigose estava associado à menor dose de CLZ em monoterapia e à boa resposta terapêutica nos pacientes com ER. Notou-se também uma associação da média da dose diária de CLZ, da gravidade sintomatológica (BPRS) e dos indivíduos do sexo feminino à super-refratariedade de resposta ao tratamento à clozapina tendo esses parâmetros uma maior distribuição no grupo dos pacientes com esquizofrenia super-refratária. Esses achados sugerem que outras estratégias de tratamento sejam avaliadas para os pacientes portadores do polimorfismo CYP2C19*17 diagnosticados com ESR, sobretudo os do sexo feminino. Futuros estudos com amostras mais alargadas seriam relevantes para dar uma maior consistência a esses achados.
2
Coller, Janet K. "The Influence of the CYP2C19 and CYP2D6 genetic polymorphisms on oxidative drug metabolism." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phc6968.pdf.
Full textAbstract:
Amendements: leaves 252-254. Copies of author's previously published articles inserted. Bibliography: leaves 226-251. The CYP2C19 and CYP2D6 genetic polymorphisms control the oxidative metabolism of many different drug classes. Populations are separated into groups of extensive metabolisers (EM), poor metabolisers (PM), and in the case of CYP2D6, ultra-rapid metabolisers (UM). In vitro studies using human liver microsomes were conducted to examine the kinetics of the oxidative metabolism of flunitrazepam, and which CYP450 enzymes mediate the oxidative metabolism of flunitrazepam, (S)-mephenytoin and proguanil.
3
Jinnai, Toshikazu. "Impact of CYP2C19 polymorphisms on the antiplatelet effect of clopidogrel in an actual clinical setting in Japan." Kyoto University, 2009. http://hdl.handle.net/2433/126458.
Full text
4
Lai, Man Po. "Single nucleotide polymorphisms of CYP2C19 gene and AHR gene and their associations to colorectal cancer and breast cancer risk in Han Chinese population /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202007%20LAI.
Full text
5
Lorberg, Caroline. "Bedeutung von Cytochrom-P450-Polymorphismen für Verlauf, Erfolg und Nebenwirkungen der Therapie mit Antidepressiva." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/15375.
Full textAbstract:
Im Bereich der medikamentösen antidepressiven Therapie ist die Bedeutung von erblichen Polymorphismen arzneistoffmetabolisierender Enzyme bereits in vielen Studien untersucht und gezeigt worden. Die meisten Antidepressiva werden über polymorphe Cytochrom-P450-Enzyme verstoffwechselt. Diese Arbeit befasst sich mit der Fragestellung, ob die Häufigkeitsverteilung der CYP2D6-, CYP2C19- und CYP2C9-Allele in der an Depression erkrankten Studienpopulation sich von der in der Normalbevölkerung unterscheidet und ob Veränderungen in der Pharmakokinetik, wie sie durch Cytochrom-P450-Polymorphismen verursacht werden, unter normalen klinischen Bedingungen Auswirkungen auf die Wirksamkeit der antidepressiven Therapie, die Nebenwirkungsrate und den Verlauf der Erkrankung haben. Im Rahmen dieser Arbeit wurden 334 Patienten auf die häufigsten CYP2D6-Allele (*3,*4,*5,*6 und Duplikation) und CYP2C19- und CYP2C9-Allele *2 und *3 mittels Genotypisierung untersucht. Die Bestimmung der seltener auftretender CYP2D6-Allele (*8,*9,*10,*17,*2 und *41) erfolgte zusätzlich bei 200 Patienten. Die entsprechenden klinischen Fragebögen mit Angaben zur Anamnese, Schwere der Erkrankung, Therapieverlauf und Nebenwirkungsprofil wurden von 233 Patienten in Abhängigkeit des CYP2D6- und CYP2C19-Genotyps ausgewertet. Für die Beurteilung des Langzeittherapieverlaufs standen jedoch deutlich weniger Patientendaten zur Verfügung, so dass die Ergebnisse zum Teil nur für den CYPD6-Genotyp ausgewertet werden konnten. Die genetischen Analysen ergaben, dass die Häufigkeitsverteilung der CYP2D6-, CYP2C19- und CYP2C9-Polymorphismen in der untersuchten Studienpopulation keine signifikante Änderung im Vergleich zur Normalbevölkerung aufwies. Während der Einfluss der CYP2D6-Genotypen auf pharmakokinetische Parameter eindeutig nachgewiesen ist, konnten die Ergebnisse dieser Arbeit weitestgehend keinen Zusammenhang zwischen der Schwere der Depression, der Therapieresponse, der Häufigkeit und Schwere der Nebenwirkungen und dem CYP2D6- und CYP2C19-Genotyp herstellen.The importance of genetic polymorphisms of drug metablizing enzymes have been already investigated und proved in many studies before. Most of antidepressants are metabolized by cytochrome P450 enzymes. The aim of this study was to determine if there is a difference in the distribution of CYP2D6-, CYP2C19- and CYP2C9-allels in inpatients with major depression in comparison to the healthy population and if changes in the pharmacokinatic, created by cytochrome P450 polymorphisms, can be have effects on the efficacy of antidepressant therapy, rate of intolerable side effects and development of the depression. We examined 334 patients by genotyping for the most important CYP2D6-allels (*3,*4,*6,*5 und duplication) and the CYP2C19- and CYP2C9-allels *2 and *3. Further 200 patients were tested for the more infrequent CYP2D6-allels (*8,*9,*10,*17,*2 and *41). The corresponding clinical questionnaires containing informations about the anamnesis, severity of the desease, therapeutic outcome and intolerable side effects have been evaluated of 233 patients in dependence of the CYP2D6- and CYP2C19-genotype. There were significant less clinical datas for the evaluation of long term therapy response be available, so that the results could be partially only analysed for the CYP2D6-genotype. The genetic analysis detected that the distribution of the CYP2D6-, CYP2C19- and CYP2C9-polymorphismen in the study population didn´t reached significant changes in comparison to the healthy population. While the influence of CYP2D6-genotypes on pharmacokinatic parameters is clear demonstrated, the results of this study mainly couldn´t establish a relation between the severity of depression, therapeutic response, frequency and severity of side effects and the CYP2D6 and CYP2C19-genotype.
6
Yang, Yu-Fan, and 楊喻帆. "Role of CYP2C19 polymorphisms in short-term rabeprazole-based triple therapy- Implication of PK/PD correlation." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/12890224878228433172.
Full text
7
洪靚娟. "Effects of CYP2C9 and CYP2C19 Polymorphisms on the Population Pharmacokinetics of Phenytoin in Taiwanese Patients with Epilepsy." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/84408275808191295749.
Full textAbstract:
碩士國立臺灣大學
臨床藥學研究所
90
Abstract Phenytoin is a commonly prescribed and effective anticonvulsant. Some patients may suffer from diplopia and ataxia under usual dose. Genetic polymorphisms of CYP2C9 and CYP2C19 may play important roles in the impairment of phenytoin hydroxylation capacity. There is still no study to evaluate the association between genetic polymorphisms of CYP2C9 and CYP2C19 and the impairment of phenytoin hydroxylation capacity in population of Taiwan. We designed a prospective study that recruited 169 patients under phenytoin treatment for more than one month. Phenytoin concentration, serum albumin, liver function test and renal function tests would be measured. We genotyped CYP2C9 and CYP2C19 polymorphisms by PCR-RFLP analysis and built NONMEM model to evaluate which factor would affect phenytoin metabolism. Our study revealed that Vmax (mg/kg/day) was 8.29 % lower in the poor metabolizers of CYP2C19 (CYP2C19 *2/ *2、CYP2C19 *2/ *3) and 36.96 % lower in the heterozygote for Leu359 allele in CYP2C9 (CYP2C9 *1/ *3), moreover, in the poor metabolizers of CYP2C19 (CYP2C19 *2/ *2、CYP2C19 *2/ *3) and heterozygote for Leu359 allele in CYP2C9 (CYP2C9 *1/ *3) was 45.75 % lower than those without the mutations in CYP2C9 and CYP2C19 genes. In respect of Km (mg/L), it was 15.09 % higher in the poor metabolizers of CYP2C19 (CYP2C19 *2/ *2、CYP2C19 *2/ *3) and 27.36 % higher in the heterozygote for Leu359 allele in CYP2C9 (CYP2C9 *1/ *3), moreover, in the poor metabolizers of CYP2C19 (CYP2C19 *2/ *2、CYP2C19 *2/ *3) and heterozygote for Leu359 allele in CYP2C9 (CYP2C9 *1/ *3) was 91.71 % higher than those without the mutations in CYP2C9 and CYP2C19 genes. Our results showed that the hydroxylation activity of phenytoin was impaired with mutations of CYP2C9 and CYP2C19. In view of the clinical use of phenytoin, three important conclusions were derived from this study: 1. The serum phenytoin concentration in patients with the CYP2C9*3 allele would increase dramatically even under low daily dose. It was necessary to monitor serum phenytoin concentrations in order to prevent adverse drug reaction. 2. Patients with CYP2C19 mutations should monitor serum phenytoin concentrations carefully under higher daily dose. 3. Figure 5-3 and figure 5-4 could be used to adjust phenytoin daily dose according to genotypes.
8
Chen, Hsiang-lan, and 陳香蘭. "Association study of polymorphisms in CYP2D6,CYP2C9and CYP2C19 genes and fluoxetine response in patients withMajor depressive disorder." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/89790059431968089891.
Full textAbstract:
碩士輔英科技大學
醫事技術系碩士班
98
Fluoxetine is a widely used antidepressant. CYP2D6, CYP2C9 and CYP2C19, three cytochrome P450 genes, are involved in the metabolism of fluoxetine and could influence clinical response. The aim of this study was to investigate the role of polymorphisms in the cytochrome P450 CYP2D6, CYP2C9 and CYP2C19 genes for fluoxetine response.There are 120 normal control and one hundred ten hospitalized patients with major depressive disorder received 20 mg/day of fluoxetine for six weeks.Symptom severity was assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17) at weeks 0, 1, 2, 3, 4 and 6. Response was defined as a reduction of 50% or more of the HAMD-17 total score following 6 weeks of treatment. In order to determine whether genetic polymorphisms at CYP2D6 , CYP2C9 and CYP2C19 is associated with major depression, PCR-RFLP and PCR product sequencing experiments were performed to identify genetic polymorphisms in CYP2D6 rs16947 and CYP2C19 rs4244285、rs4986893 of major depression patients and unrelated of non-major depression subjects blood.A total of 65 (59.1%) of the 110 completers were classified as responders after six weeks of treatment. There are no significant differences between the responders and nonresponder with respect to sex (p = 0.10), age (p = 0.48), age onset of major depressive episode (p = 0.19), numbers of previous episode (p =0.12) and baseline HAMD-17 scores (p = 0.31). No associations with CYP2D6*2 (2850C>T), CYP2C19*2 (681G>A), or CYP2C19*3 (636G>A) genes polymorphisms and the response to fluoxetine were found (p = 0.695, p = 0.948, and p =0.894 respectively) . These results suggest that the polymorphisms of CYP2D6*2, CYP2C19*2 and CYP2C19*3 genes should be unlikely to play a major role in the fluoxetine response. Nevertheless, methodological and sample size limitations of this study do not allow definitive conclusions.
9
Wu, Ying-Ying, and 吳盈瑩. "The relationship of drug plasma concentrations, and genetic polymorphisms of CYP2C9, CYP2C19, CYP2C18 and HLA in phenytoin hypersensitivity." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/39189959435269285882.
Full textAbstract:
碩士國立陽明大學
藥理學研究所
98
Drug hypersensitivity is a common adverse event during medical treatments and contributes to ~20% reported adverse drug reactions (ADRs). These hypersensitivity reactions may present from mild skin rash (MPE) to life-threatening drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN). Many aromatic antiepileptic drugs (AEDs), such as phenytoin, carbamazepine or lamotrigine, are frequently associated with hypersensitive reactions. In particular, phenytoin is a first-line AED, however, more than 19% patients received phenytoin developed hypersensitivity reactions. The previous studies showed that the deficiency of microsomal epoxide hydroxylase and human leukocyte antigen (HLA) subtypes may associate with AED hypersensitivity. However, the relationship between drug metabolism/genetic susceptibility and phenytoin-induced hypersensitivity reactions is still unclear. To investigate whether genetic polymorphisms of phenytoin metabolic enzymes, including CYP2C9, CYP2C19 and CYP2C18, are associated with phenytoin hypersensitivity, a total of 157 phenytoin-hypersensitvity patients have been enrolled, including 54 phenytoin-SJS/TEN cases, 27 phenytoin-DRESS cases and 78 phenytoin-MPE/other hypersensitivity reactions cases. 118 tolerant subjects who received phenytoin more than 3 months without adverse reactions were enrolled as the control group. The data showed that CYP2C9*3 have a strong association with phenytoin-induced hypersensitivity; there are 30.2% of phenytoin-SJS/TEN, 37.5% of phenytoin-DRESS, and 14.7% of phenytoin-MPE or other hypersensitivity reactions cases carry this mutant allele, CYP2C9*3 (I359L), which causes deficient enzyme activity. In comparison, only 2.5% patients in the tolerant control group carry CYP2C9*3. Moreover, other alleles with poor metabolic reactions, such as CYP2C19*2 (G681A) and CYP2C19*3 (G636A), were also found in both case and control groups, though these single nucleotide polymorphisms do not show significant association with phenytoin-induced hypersensitivity. To investigate the relationship between plasma concentration of drug and hypersensitivity reactions, the level of phenytoin in the acute stage of patients and its kinetic change after withdrawing phenytoin were determined. The data revealed that both SJS/TEN, and MPE case groups have poorer metabolic ability and keep higher phenytoin concentration after withdrawing drug. In addition, the HLA-A, HLA-B and HLA-DRB1 genotypes were determined and compared between case and control groups. HLA-B*1301, HLA-B*1502, HLA-B*4609, HLA-B*5101, HLA-DRB1*1001 and HLA-DRB1*1502 showed significant association with phenytoin-induced hypersensitivity. In conclusion, these data revealed that the genetic polymorphisms of CYP2C9, the phenytoin plasma levels, and HLA genotypes all contribute to phenytoin-hypersensitivity.
10
Gültepe, Şenol. "Auswirkungen von CYP2D6-, CYP2C9- und CYP2C19-Polymorphismen auf Pharmakokinetik und Wirkungen von Carvedilol." Doctoral thesis, 2011. http://hdl.handle.net/11858/00-1735-0000-000D-F1DE-2.
Full textConference papers on the topic "CYP2C19-polymorphisms"
1
Лифшиц, Г., G. Lifshic, Е. Зеленкская, E. Zelenkskaya, Н. Сараева, N. Saraeva, Анна Горохова, Anna Gorokhova, Константин Апарцин, and Konstantin Apartsin. "Association of polymorphisms Gene CYP2C19 with endpoints of efficacy and safety of clopidogrel therapy And platelet aggregation in patients with acutecoronary syndrome study Protocol." In Topical issues of translational medicine: a collection of articles dedicated to the 5th anniversary of the day The creation of a department for biomedical research and technology of the Irkutsk Scientific Center Siberian Branch of RAS. Москва: INFRA-M Academic Publishing LLC., 2017. http://dx.doi.org/10.12737/conferencearticle_58be81ec9680e.
Full textAbstract:
Aim: to reveal the association of gene CYP2C19 polymorphisms and efficacy and safety endpoints of clopidogrel therapy in patients with acute coronary syndrome. Materials and methods. A total of 431 patients with acute coronary syndrome undergoing coronary stent placement was studied. CYP2C19 polymorphisms (*2, *3, *17) were evaluated, platelet aggregation with ADP and efficacy and safety for 30 days after coronary stent placement was studied. Results. Within the selected patients there was no significant association between carriage of at least one allele of the CYP2C19*2, and/or CYP2C19*3 and paradoxical response to clopidogrel. Significant association between carriage of allele CYP2C19*17 and the presence of bleeding was detected. The algorithm for selection of individual drug therapy for patients receiving clopidogrel therapy was developed. Conclusion. The results can be extremely important for decision-making about the strategy of dual antiplatelet therapy and the tactics of choice of drugs.
2
Villalobos-Torres, L., X. Díaz-Villamarín, C. Dávila-Fajardo, M. Valle-Corpas, and J. Cabeza-Barrera. "CP-011 Influence of surgical strategy and baseline conditions versus cyp2c19 polymorphisms in antiplatelet response to clopidogrel in patients undergoing percutaneus transluminal angioplasty." In 22nd EAHP Congress 22–24 March 2017 Cannes, France. British Medical Journal Publishing Group, 2017. http://dx.doi.org/10.1136/ejhpharm-2017-000640.11.
Full text