Academic literature on the topic 'Transcripción genética'

Heat stress is one of the main causes of low conception rate in Bos taurus cows in a tropical climate. On the other hand, in this environment, oocytes from Bos indicus show greater developmental capacity after in vitro fertilization than those from Bos taurus, suggesting an adaptation to the hot climate. Heat shock proteins (HSP) are chaperones that promote protection against heat damage, and their transcription is associated to stress. The aim of this study was to evaluate the expression of HSP70-1 gene (Genbank NM174550), a member of HSP family, in oocytes from Bos taurus (Holstein) and Bos indicus (Gyr) cows raised in the tropical climate located at 21�35′′S latitude, 43�51′′W longitude, and 435 m altitude. Cumulus–oocyte complexes were recovered by oocyte pickup from mature non-lactating Holstein (n = 4) and Gyr (n = 4) donor cows during the hot season. Cumulus cells of viable oocytes were removed by vortexing in TALP-HEPES plus BSA, and pools (3 for each breed) with 12 immature oocytes were rapidly frozen in liquid nitrogen and subsequently thawed for RNA extraction. Total RNA extraction was performed using Rneasy� Micro kit (Qiagen, Valencia, CA, USA), and first strands were synthesized using SuperscriptTM III First Strand Synthesis kit (Invitrogen, Chicago, IL, USA). Relative quantification was performed in duplicate using real-time PCR (ABI Prism� 7000; Applied Biosystems, Foster City, CA, USA); reactions consisted of a mixture of iTaqTM SYBR� Green Supermix with ROX (Bio-Rad, Waltham, MA, USA) and cDNA equivalent to 1.2 oocytes and gene specific primers. Expression of the GAPDH gene was used as endogenous reference. Calculations of relative quantification were performed by the comparative Ct method, using the lowest value found in Bos indicus oocytes as calibrator; values (mean � SE) are shown as n-fold difference relative to the calibrator. Statistical comparison between breeds was performed by analysis of variance. Oocytes from Holstein cows showed a higher level (P < 0.05) of HSP70-1 expression (1.82 � 0.22) than oocytes recovered from Gyr cows (1.12 � 0.11). Previous study reported that oocytes from Gyr cows in a tropical climate showed a higher blastocyst rate after in vitro fertilization than Holstein oocytes (Camargo et al. 2006 Reprod. Fertil. Dev. 18, 243 abst). The lower level of HSP70-1 in Gyr oocytes suggests that they were less subject to stress than the Holstein ones, which may reflect their capacity to develop after fertilization. This effect may be, at least in part, due to the ability of Bos indicus cows to regulate body temperature in a hot environment, causing less stress on oocytes. Financial support was provided by FAPEMIG, MG, Brazil, and CNPq, DF, Brazil. Thanks to Agrogen�tica, Vi�osa, Brazil, for the real-time PCR machine.

ABSTRACT Ehrlichia ruminantium, an obligate intracellular bacterium transmitted by ticks of the genus Amblyomma, causes heartwater disease in ruminants. The gene coding for the major antigenic protein MAP1 is part of a multigene family consisting of a cluster containing 16 paralogs. In the search for differentially regulated genes between E. ruminantium grown in endothelial and tick cell lines that could be used in vaccine development and to determine if differences in the map1 gene cluster exist between different isolates of E. ruminantium, we analyzed the map1 gene cluster of the Senegal and Gardel isolates of E. ruminantium. Both isolates contained the same number of genes, and the same organization as found in the genome sequence of the Welgevonden isolate (H. Van Heerden, N. E. Collins, K. A. Brayton, C. Rademeyer, and B. A. Allsopp, Gene 330:159-168, 2004). However, comparison of two subpopulations of the Gardel isolate maintained in different laboratories demonstrated that recombination between map1-3 and map1-2 had occurred in one subpopulation with deletion of one entire gene. Reverse transcription-PCR on E. ruminantium derived mRNA from infected cells using gene-specific primers revealed that all 16 map1 paralogs were transcribed in endothelial cells. In one vector (Amblyomma variegatum) and several nonvector tick cell lines infected with E. ruminantium, transcripts were found for between 4 and 11 paralogs. In all these cases the transcript for the map1-1 gene was detected and was predominant. Our results indicate that the map1 gene cluster is relatively conserved but can be subject to recombination, and differences in the transcription of map1 multigenes in host and vector cell environments exist.

Abstract Background Treatment failures in cancers, including multiple myeloma (MM), are most likely due to the persistence of a minor population of tumor-initiating cells (TICs), which are noncycling or slowly cycling and very drug resistant. Methods Gene expression profiling and real-time quantitative reverse transcription polymerase chain reaction were employed to define genes differentially expressed between the side-population cells, which contain the TICs, and the main population of MM cells derived from 11 MM patient samples. Self-renewal potential was analyzed by clonogenicity and drug resistance of CD24+ MM cells. Flow cytometry (n = 60) and immunofluorescence (n = 66) were applied on MM patient samples to determine CD24 expression. Therapeutic effects of CD24 antibodies were tested in xenograft MM mouse models containing three to six mice per group. Results CD24 was highly expressed in the side-population cells, and CD24+ MM cells exhibited high expression of induced pluripotent or embryonic stem cell genes. CD24+ MM cells showed increased clonogenicity, drug resistance, and tumorigenicity. Only 10 CD24+ MM cells were required to develop plasmacytomas in mice (n = three of five mice after 27 days). The frequency of CD24+ MM cells was highly variable in primary MM samples, but the average of CD24+ MM cells was 8.3% after chemotherapy and in complete-remission MM samples with persistent minimal residual disease compared with 1.0% CD24+ MM cells in newly diagnosed MM samples (n = 26). MM patients with a high initial percentage of CD24+ MM cells had inferior progression-free survival (hazard ratio [HR] = 3.81, 95% confidence interval [CI] = 5.66 to 18.34, P < .001) and overall survival (HR = 3.87, 95% CI = 16.61 to 34.39, P = .002). A CD24 antibody inhibited MM cell growth and prevented tumor progression in vivo. Conclusion Our studies demonstrate that CD24+ MM cells maintain the TIC features of self-renewal and drug resistance and provide a target for myeloma therapy.

Abstract Background Genetic resistance in cattle is considered a suitable way to control tick burden and its consequent losses for livestock production. Exploring tick-resistant (R) and tick-susceptible (S) hosts, we investigated the genetic mechanisms underlying the variation of Braford resistance to tick infestation. Skin biopsies from four-times-artificially infested R (n = 20) and S (n = 19) hosts, obtained before the first and 24 h after the fourth tick infestation were submitted to RNA-Sequencing. Differential gene expression, functional enrichment, and network analysis were performed to identify genetic pathways and transcription factors (TFs) affecting host resistance. Results Intergroup comparisons of hosts before (Rpre vs. Spre) and after (Rpost vs. Spost) tick infestation found 51 differentially expressed genes (DEGs), of which almost all presented high variation (TopDEGs), and 38 were redundant genes. Gene expression was consistently different between R and S hosts, suggesting the existence of specific anti-tick mechanisms. In the intragroup comparisons, Rpost vs. Rpre and Spost vs. Spre, we found more than two thousand DEGs in response to tick infestation in both resistance groups. Redundant and non-redundant TopDEGs with potential anti-tick functions suggested a role in the development of different levels of resistance within the same breed. Leukocyte chemotaxis was over-represented in both hosts, whereas skin degradation and remodeling were only found in TopDEGs from R hosts. Also, these genes indicated the participation of cytokines, such as IL6 and IL22, and the activation of Wingless (WNT)-signaling pathway. A central gene of this pathway, WNT7A, was consistently modulated when hosts were compared. Moreover, the findings based on a genome-wide association study (GWAS) corroborate the prediction of the WNT-signaling pathway as a candidate mechanism of resistance. The regulation of immune response was the most relevant pathway predicted for S hosts. Members of Ap1 and NF-kB families were the most relevant TFs predicted for R and S, respectively. Conclusion This work provides indications of genetic mechanisms presented by Braford cattle with different levels of resistance in response to tick infestation, contributing to the search of candidate genes for tick resistance in bovine.

Abstract During a parasitological survey of fishes at Iguazu National Park, Argentina, specimens belonging to the allocreadiid genus Auriculostoma were collected from the intestine of Characidium heirmostigmata. The erection of the new species is based on a unique combination of morphological traits as well as on phylogenetic analysis. Auriculostoma guacurarii n. sp. resembles four congeneric species – Auriculostoma diagonale, Auriculostoma platense, Auriculostoma tica and Auriculostoma totonacapanensis – in having smooth and oblique testes, but can be distinguished by a combination of several morphological features, hosts association and geographic distribution. Morphologically, the new species can be distinguished from both A. diagonale and A. platense by the egg size (bigger in the first and smaller in the last); from A. tica by a shorter body length, the genital pore position and the extension of the caeca; and from A. totonacapanensis by the size of the oral and ventral sucker and the post-testicular space. Additionally, one specimen of Auriculostoma cf. stenopteri from the characid Charax stenopterus (Characiformes) from La Plata River, Argentina, was sampled and the partial 28S rRNA gene was sequenced. The phylogenetic analysis revealed that A. guacurarii n. sp. clustered with A. tica and these two as sister taxa to A. cf. stenopteri. The new species described herein is the tenth species in the genus and the first one parasitizing a member of the family Crenuchidae.

ABSTRACT SFTS phlebovirus (SFTSV) is an emerging tick-borne bunyavirus that was first reported in China in 2009. Here we report the generation of a recombinant SFTSV (rHB29NSsKO) that cannot express the viral nonstructural protein (NSs) upon infection of cells in culture. We show that rHB29NSsKO replication kinetics are greater in interferon (IFN)-incompetent cells and that the virus is unable to suppress IFN induced in response to viral replication. The data confirm for the first time in the context of virus infection that NSs acts as a virally encoded IFN antagonist and that NSs is dispensable for virus replication. Using 3′ rapid amplification of cDNA ends (RACE), we mapped the 3′ end of the N and NSs mRNAs, showing that the mRNAs terminate within the coding region of the opposite open reading frame. We show that the 3′ end of the N mRNA terminates upstream of a 5′-GCCAGCC-3′ motif present in the viral genomic RNA. With this knowledge, and using virus-like particles, we could demonstrate that the last 36 nucleotides of the NSs open reading frame (ORF) were needed to ensure the efficient termination of the N mRNA and were required for recombinant virus rescue. We demonstrate that it is possible to recover viruses lacking NSs (expressing just a 12-amino-acid NSs peptide or encoding enhanced green fluorescent protein [eGFP]) or an NSs-eGFP fusion protein in the NSs locus. This opens the possibility for further studies of NSs and potentially the design of attenuated viruses for vaccination studies. IMPORTANCE SFTS phlebovirus (SFTSV) and related tick-borne viruses have emerged globally since 2009. SFTSV has been shown to cause severe disease in humans. For bunyaviruses, it has been well documented that the nonstructural protein (NSs) enables the virus to counteract the human innate antiviral defenses and that NSs is one of the major determinants of virulence in infection. Therefore, the use of reverse genetics systems to engineer viruses lacking NSs is an attractive strategy to rationally attenuate bunyaviruses. Here we report the generation of several recombinant SFTS viruses that cannot express the NSs protein or have the NSs open reading frame replaced with a reporter gene. These viruses cannot antagonize the mammalian interferon (IFN) response mounted to virus infection. The generation of NSs-lacking viruses was achieved by mapping the transcriptional termination of two S-segment-derived subgenomic mRNAs, which revealed that transcription termination occurs upstream of a 5′-GCCAGCC-3′ motif present in the virus genomic S RNA.

Many studies have demonstrated that cancer stem cells (CSCs) or tumor-initiating cells (TICs) are responsible for tumor cell proliferation, chemotherapy resistance, metastasis, and relapse in various cancers. We, and others, have previously shown that the signal transducer and activator of transcription 3 (STAT3) signaling pathway is responsible for CSCs and TICs growth. Recent reports have indicated that the heat shock protein 90 (Hsp90) is also essential for the survival of CSCs and TICs. SNX-2112 is an Hsp90 inhibitor. However, it remains unclear whether proliferation of esophageal cancer stem-like cells (ECSLCs) is suppressed by SNX-2112 with knockdown of STAT3 (shSTAT3). Here, we explored the association between SNX-2112 with shSTAT3 and the suppression of ECSLCs growth. We found that the expression level of both STAT3 and p-STAT3 was higher in clinical esophageal cancer tissue than in the adjacent normal tissue, using western blot and qPCR analysis. Furthermore, differential expression analysis demonstrated that STAT3 was overexpressed in clinical specimens. We demonstrated that SNX-2112 inhibited cancer cell proliferation, decreased ABCB1 and ABCG2 gene expression levels and reduced the colony formation capacity of ECSLCs, which was enhanced by STAT3 silencing. Flow cytometry analysis revealed that the combination of SNX-2112 and shSTAT3 significantly induced apoptosis and cell cycle arrest at G2/M phase in ECSLCs. Levels of proliferation pathway proteins, including p38, c-Jun N-terminal kinase (JNK), and extracellular signal–regulated kinase (ERK) which were also client proteins of Hsp90, were also reduced. In addition, SNX-2112 with shSTAT3 inhibited the proliferation of ECSLCs in vivo. Finally, STAT3 overexpression eliminated the apoptotic and antiproliferative effects of SNX-2112 on ECSLCs. Hence, these results provide a rationale for the therapeutic potential of the combination of SNX-2112 with shSTAT3 in esophageal cancer, and may indicate new targets for clinical intervention in human cancer.

Many studies have demonstrated that cancer stem cells (CSCs) or tumor-initiating cells (TICs) are responsible for tumor cell proliferation, chemotherapy resistance, metastasis, and relapse in various cancers. We, and others, have previously shown that the signal transducer and activator of transcription 3 (STAT3) signaling pathway is responsible for CSCs and TICs growth. Recent reports have indicated that the heat shock protein 90 (Hsp90) is also essential for the survival of CSCs and TICs. SNX-2112 is an Hsp90 inhibitor. However, it remains unclear whether proliferation of esophageal cancer stem-like cells (ECSLCs) is suppressed by SNX-2112 with knockdown of STAT3 (shSTAT3). Here, we explored the association between SNX-2112 with shSTAT3 and the suppression of ECSLCs growth. We found that the expression level of both STAT3 and p-STAT3 was higher in clinical esophageal cancer tissue than in the adjacent normal tissue, using western blot and qPCR analysis. Furthermore, differential expression analysis demonstrated that STAT3 was overexpressed in clinical specimens. We demonstrated that SNX-2112 inhibited cancer cell proliferation, decreased ABCB1 and ABCG2 gene expression levels and reduced the colony formation capacity of ECSLCs, which was enhanced by STAT3 silencing. Flow cytometry analysis revealed that the combination of SNX-2112 and shSTAT3 significantly induced apoptosis and cell cycle arrest at G2/M phase in ECSLCs. Levels of proliferation pathway proteins, including p38, c-Jun N-terminal kinase (JNK), and extracellular signal–regulated kinase (ERK) which were also client proteins of Hsp90, were also reduced. In addition, SNX-2112 with shSTAT3 inhibited the proliferation of ECSLCs in vivo. Finally, STAT3 overexpression eliminated the apoptotic and antiproliferative effects of SNX-2112 on ECSLCs. Hence, these results provide a rationale for the therapeutic potential of the combination of SNX-2112 with shSTAT3 in esophageal cancer, and may indicate new targets for clinical intervention in human cancer.

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Ewing s sarcoma was first described by James Ewing in 1921 and it is the second most common bone tumor in children and young adults. Both chromosomal breakage and translocation occur in this sarcoma. The EWS gene is localized in chromosome 22 and is involved in this translocation. However, little is known about this gene breaking region and what sequences could be involved in higher chromosomal break susceptibility. In this study we aimed to investigate three SNPs in the EWS gene breaking region in a healthy subjects population and in Ewing s sarcoma patients. Genotyping was performed by TaqMan? assay for allelic discrimination using Real-Time PCR System. We conducted analysis of allelic and genotypic frequencies, as well as association and transmission disequilibrium tests. According to our results, the control group showed similar and different genotypes distribution of all SNPs when compared to other populations studied by different projects, which shows how important it is to know the frequencies of our population. To test the hypothesis that some SNP, SNParrangement or haplotype could influence in the susceptibility to develop Ewing s sarcoma, we compared affected with non-affected individuals using association studies. The results showed one significant difference: a higher presence of homozygote T-rs4820804 in Ewing s Sarcoma patients. Transmission Disequilibrium Test (TDT) was performed to compare data from Ewing s Sarcoma patients and from their families but no statistically significant result was found. In conclusion, we find that the TT-rs4820804 EWS genotype can be associate with Ewing s sarcoma and that the rs4820804 SNP can be a candidate to understand the EWS breakage susceptibility.
O sarcoma de Ewing foi primeiramente descrito por James Ewing em 1921 e ? o segundo tumor ?sseo mais frequente em crian?as, adolescente e adultos jovens. Neste sarcoma, ? comum ocorrer a quebra e a transloca??o cromoss?mica. Dentre os genes envolvidos nesta transloca??o est? o gene EWS, localizado no cromossomo 22. Entretanto, pouco se sabe a respeito da regi?o de quebra deste gene e quais sequ?ncias poderiam levar a uma maior susceptibilidade a quebra cromoss?mica. Sendo assim, o objetivo deste trabalho foi investigar tr?s polimorfismos de base ?nica (SNPs) presentes na regi?o de quebra do gene EWS, em uma popula??o de indiv?duos saud?veis e em pacientes afetados pelo Sarcoma de Ewing. A genotipagem para os SNPs selecionados foi realizada usando TaqMan SNP Genotyping Assay pelo sistema de PCR em tempo real. N?s realizamos an?lises de frequ?ncias al?licas e genot?picas, assim como um estudo de associa??o e de desequil?brio de transmiss?o. A compara??o das frequ?ncias al?licas e genot?picas entre as popula??es deste estudo e entre popula??es de projetos j? publicados mostrou particularidades entre as popula??es, revelando a import?ncia de se conhecer tais frequ?ncias na popula??o de estudo. Para testar a hip?tese de que algum SNP, hapl?tipo ou combina??o espec?fica de SNPs poderia influenciar na susceptibilidade ao Sarcoma de Ewing, comparamos afetados com n?o-afetados realizando estudos de associa??o cujos resultados mostraram uma ?nica diferen?a significativa: a maior incid?ncia no gen?tipo TT-rs4820804 entre os afetados pelo Sarcoma de Ewing. O Teste de Desequil?brio de Transmiss?o (TDT) comparou os dados dos pacientes afetados e os dados de seus familiares, mas nenhum resultado significativo foi encontrado. Em conclus?o, o gen?tipo TT-rs4820804 pode estar associado ao Sarcoma de Ewing e o SNP rs4820804 pode ser candidato para aux?lio do entendimento da susceptibilidade de quebra do gene EWS.

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In this study the SNPs rs640098, rs491714, rs611307 into the FLI1 gene were genotyped in a sample of 201 subjects from southern Brazilian population, in 24 Ewing s sarcoma patients (geographically matched with control group) and 54 of their family members, including parents and siblings. We performed association studies comparing genotypic frequencies of rs640098, rs491714, rs611307 into the FLI1 gene, and all possible genotype combinations between Ewing s Sarcoma patients and control group. Of the three SNPs investigated individually, only one of them showed a significant result when compared to the control group; our non-combined analysis revealed a significantly higher presence of homozygote A-rs497714 among Ewing s Sarcoma patients (p=0.0065; Chi square Test). In all other tested clusters, we always noticed a higher rate of homozygote A-rs497714 among Ewing s Sarcoma patients independent of the other SNP-arrangements and/or haplotype combinations. In addition, we performed transmission disequilibrium tests comparing data from Ewing s Sarcoma patients and from their families (parents and siblings), but no statistically significant result was found. In conclusion, the present study provides evidence statistically founded that the AA-rs497714 FLI1 genotype can associated with Ewing's sarcoma. And that this polymorphism can be clinically useful as a potential genetic marker to the prognostic of risk to develop this cancer or to provide insights into FLI1 chromosome breakage context of tumorigenesis.
Neste estudo, os SNPs rs640098, rs491714, rs611307 no gene FLI1 foram genotipados em uma amostra de 201 indiv?duos da popula??o do sul do Brasil, e em 24 pacientes portadores de Sarcoma Ewing (geograficamente comparado com grupo controle) e 54 de seus familiares, incluindo pais e irm?os. Realizamos estudos de associa??o, comparando as freq??ncias genot?picas do rs640098 e rs491714 e rs611307 no gene FLI1, e todas as combina??es poss?veis entre o gen?tipo de pacientes Sarcoma de Ewing e grupo controle. Dos tr?s SNPs investigados individualmente, apenas um deles apresentou um resultado significativo quando comparado com o grupo controle; nossa an?lise n?o-combinada revelou uma presen?a significativamente maior de homozigoto A-rs497714 entre os pacientes de Sarcoma Ewing (p = 0,0065; Chi quadrado). Em todos os outros grupos testados, foi notada uma maior taxa de homozigoto A-rs497714 entre os pacientes com Sarcoma de Ewing, independentemente dos outros arranjos e / ou combina??es de SNP e hapl?tipos. Al?m disso, foram realizados testes de desequil?brio de transmiss?o, comparando dados de pacientes portadores de Sarcoma de Ewing e de suas fam?lias (pais e irm?os), mas nenhum resultado estatisticamente significativo foi encontrado. Em conclus?o, o presente estudo fornece evid?ncias estatisticamente fundada de que o gen?tipo AA-rs497714 FLI1 pode associado ao sarcoma de Ewing. E que este polimorfismo pode ser clinicamente ?til como um potencial marcador gen?tico para o progn?stico de risco para desenvolver este c?ncer ou para fornecer insights no contexto de quebras cromoss?micas de tumorig?nese no gene FLI1.

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Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq
After the proceeding of a transplant, it is of huge concem the use of all therapeutic resource available in order to prevent graft rejection. The incidence and severity of acute rejection have been reduced along time due to the development of new immunosuppressive agents such as cyclosporin, tacrolimus, mycophenolate mofetil (MMF), specific polyclonal and monoclonal antibodies. Mofetil mycophenolate (MMF) is a prodrug active only after its hydrolysis to mycophenolic acid (MPA). Once it, has a large variability on inter-individual response, an increasing need of therapeutic monitoring arises. This will permit an individualization of MMF therapy, optimizing immunosuppression and minimizing potential toxic effects.The aim of pharmacogenetics is to evaluate the association between individual genetic characteristics and different responses to the same therapeutic regimen. When considering immunosuppressive drugs, genetic changes on a single nucleotide (single nucleotide polymorphisms - SNPs) of genes encoding proteins involved in transport or drug metabolism may affect patient?s response to therapy. UDP-glucuronosyltransferases (UGTs) belong to a group of enzymes involved in phase II reactions, responsible for the detoxification of endogenous and exogenous substrates. UGT1A9 is of particular interest once it is the primary enzyme involved in the metabolism of the MPA. This enzyme is encoded by the UGT1A9 gene.In the present study, we investigated the effect of UGT1A9 c.98T>C (rs72551330; g. 87289T>C) allelic variants on MMF metabolism in 39 renal transplant volunteers. MPA levels were measured by high pressure liquid chromatography using ultraviolet detection (HPLC/UV). The analysis of c.98T>C polymorphism was performed by polymerase chain reaction (PCR), followed by fragment purification and sequencing. All investigated individuals showed having the same polymorphism genotype (c.98TT) evaluation of variants or genotype influence on plasma levels of MPA and MPAG was not possible, even though different levels were observed in the study.
Ao realizar um transplante, ? de fundamental import?ncia que, seja utilizado todo o arsenal terap?utico dispon?vel e cuidados para evitar a rejei??o do enxerto. A incid?ncia e a intensidade da rejei??o aguda t?m sido reduzidas gra?as ao uso de f?rmacos imunossupressores, como ciclosporina, tacrolimus, micofenolato de mofetil (MMF), anticorpos monoclonais e policlonais. O MMF ? um pr?-f?rmaco com atividade ap?s sua hidr?lise a ?cido micofen?lico (MPA). No entanto, possui grande variabilidade inter-individual de resposta e por isso ? crescente a import?ncia da realiza??o de seu monitoramento terap?utico, o qual permite individualizar a dose de MMF e otimizar a imunossupress?o, minimizando os potenciais efeitos t?xicos. A farmacogen?tica estuda a rela??o entre as caracter?sticas gen?ticas do indiv?duo e as diferentes respostas a uma mesma terapia farmacol?gica.No caso de f?rmacos imunossupressores, altera??es gen?ticas de um ?nico nucleot?deo (single nucleotide polymorphisms - SNPs) em genes que codificam prote?nas envolvidas no transporte ou no metabolismo do f?rmaco podem modificar a resposta do paciente ? terap?utica. As UDP-glucuronosiltransferases (UGTs) pertencem a um grupo de enzimas envolvidas na fase II, respons?vel pela detoxifica??o de subst?ncias end?genas e ex?genas. A UGT1A9 ? de especial interesse por ser a principal enzima envolvida no metabolismo do ?cido micofen?lico. Esta enzima ? codificada pelo gene UGT1A9. No presente estudo, foi investigado o efeito das variantes al?licas de UGT1A9 c.98T>C (rs72551330; g. 87289T>C) no metabolismo de MMF em 39 pacientes volunt?rios transplantados renais.Foram dosados os n?veis de MPA por cromatografia l?quida de alta efici?ncia utilizando detec??o com ultravioleta (HPLC/UV) e a an?lise do polimorfismo c.98T>C do gene UGT1A9 foi realizada utilizando rea??o em cadeia de polimerase (PCR), seguida de purifica??o do fragmento e sequenciamento. Todos os indiv?duos investigados apresentaram o mesmo gen?tipo (c.98TT) para este polimorfismo, n?o possibilitando a avalia??o da influ?ncia das variantes ou gen?tipos deste polimorfismo sobre os n?veis plasm?ticos de MPA e MPAG, apesar de n?veis diversos destes compostos terem sido identificados nos pacientes.