Dataset Information

The impact of polymorphisms in STAT6 on treatment outcome in HCV infected Taiwanese Chinese.

ABSTRACT: Genetic polymorphisms observed in various disease states associated with sensitivity or resistance to specific treatments have been a robust area of investigation for decades, with the potential to allow clinicians to make evidence-based decisions on the appropriate course of treatment. This study aimed to evaluate whether genetic polymorphisms of the signal transducer and activator of transcription 6 gene (STAT6) could be associated with a sustained virological response (SVR) among patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2) who were treated with peginterferon plus ribavirin (PEG-IFN?-RBV). We analyzed the associations between SVR to PEG-IFN?-RBV therapy and 4 single nucleotide polymorphisms (SNPs) in STAT6. This study included Taiwanese Chinese patients infected with either HCV-1 (n?=?265) or HCV-2 (n?=?195) in the presence or absence of an SVR. Among the STAT6 SNPs examined, the dosage effect of the A allele and allele frequency in rs1059513 were inversely correlated with SVR in patients infected with HCV-1 (P?=?0.0179 and P?=?0.0235, respectively). This effect was not observed in patients infected with HCV-2. The GG, GGG, and GGGC STAT6 haplotypes comprising 2, 3, and 4 SNPs (rs1059513, rs703817, rs324015, and rs3024974) were found to be associated with SVR, and their presence may increase the probability of a successful treatment outcome in patients infected with HCV-1 (P?=?0.0273, 0.0352, and 0.0368, respectively). Moreover, a multivariate logistic regression model for predicting an SVR revealed that the presence of the GGGC haplotype carriers mutually affected the outcome of PEG-IFN?-RBV treatment. The presence of STAT6 SNPs and the association with SVR demonstrated that STAT6 polymorphisms might influence the therapeutic outcomes of patients infected with HCV-1 under standard-of-care (SOC) treatment.

SUBMITTER: Lim YP

PROVIDER: S-EPMC3654984 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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The impact of polymorphisms in STAT6 on treatment outcome in HCV infected Taiwanese Chinese.

Lim Yun-Ping YP Hsu Yu-An YA Tsai Kun-Hsi KH Tsai Fuu-Jen FJ Peng Cheng-Yuan CY Liao Wen-Ling WL Hung Dong-Zong DZ Tien Ni N Lin Chien-Yih CY Wan Lei L

BMC immunology 20130508

Genetic polymorphisms observed in various disease states associated with sensitivity or resistance to specific treatments have been a robust area of investigation for decades, with the potential to allow clinicians to make evidence-based decisions on the appropriate course of treatment. This study aimed to evaluate whether genetic polymorphisms of the signal transducer and activator of transcription 6 gene (STAT6) could be associated with a sustained virological response (SVR) among patients inf ...[more]

PMID: 23651608

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Project description:BACKGROUND:CD40, encoded by TNFRSF5, participates in the survival of B cells, process of antigen presentation and generation of CD8+ T cell memory. It also has an important effect on HCV antiviral immune response. This study aims to investigate whether TNFRSF5 gene polymorphisms are associated with HCV infection outcomes among Chinese population. METHODS:Three single nucleotide polymorphism (SNPs) (rs1535045, rs1883832, rs4810485) on TNFRSF5 were genotyped by TaqMan assay among Chinese population, including 1513 uninfected subjects, 496 spontaneous viral clearance subjects and 768 persistent HCV-infected subjects. Logistic analysis was used to compare these SNPs among different groups in this cross-sectional study. Functional annotations of the identified SNPs were further evaluated by bioinformatics analysis. RESULTS:After adjusted by age, gender and routes of infection, the results of logistic analysis indicated that individuals carrying rs1535045 T allele had a higher risk to infect HCV compared with C allele (in recessive model, adjusted OR?=?1.368, 95%CI?=?1.070-1.749, P?=?0.012). Subjects carried rs1535045 TT genotype were more likely to infect HCV than wild CC genotype (adjusted OR?=?1.397, 95%CI?=?1.078-1.809, P?=?0.011). For rs1883832, T allele was significantly associated with an increased risk of HCV infection (in recessive model, adjusted OR?=?1.337, 95%CI?=?1.069-1.673, P?=?0.011). Subjects with TT genotype had more possibility to infect HCV (adjusted OR?=?1.351, 95%CI?=?1.060-1.702, P?=?0.015). In the stratified analysis, rs1535045 and rs1883832 were remained in various subgroups and the heterogeneity test showed no pronounced heterogeneity in any pairwise comparison (all P?>?0.05). In addition, the results of the cumulative effects showed a tendency of that the more risk alleles (rs1535045 T and rs1883832 T) subjects carried, the more possibility of HCV infection exhibited (P<0.001). In haplotype analyses, compared with the CC haplotype, CT, TC and TT was correlated with an increased risk to infect HCV (P?=?0.029, P?=?0.047 and P<0.001, respectively). CONCLUSIONS:In conclusion, CD40 polymorphisms were significantly associated with the susceptibility to HCV among Chinese populations.

Dataset Information

The impact of polymorphisms in STAT6 on treatment outcome in HCV infected Taiwanese Chinese.

Publications

The impact of polymorphisms in STAT6 on treatment outcome in HCV infected Taiwanese Chinese.

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