Department of Pharmacy, College of Pharmacy, China Medical University, Taichung 40402, Taiwan.
BMC Immunol. 2013 May 8;14:21. doi: 10.1186/1471-2172-14-21.
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-IFNα-RBV). We analyzed the associations between SVR to PEG-IFNα-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-IFNα-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.
在与对特定治疗的敏感性或耐药性相关的各种疾病状态中观察到的遗传多态性是几十年来研究的一个活跃领域，具有使临床医生能够根据适当的治疗方案做出基于证据的决策的潜力。本研究旨在评估信号转导和转录激活因子 6 基因（STAT6）的遗传多态性是否与感染丙型肝炎病毒基因型 1 和 2（HCV-1 和 HCV-2）的患者的持续病毒学应答（SVR）相关，这些患者接受了聚乙二醇干扰素加利巴韦林（PEG-IFNα-RBV）治疗。我们分析了 SVR 与 STAT6 中 4 个单核苷酸多态性（SNP）之间的关联。这项研究包括在存在或不存在 SVR 的情况下，感染 HCV-1（n=265）或 HCV-2（n=195）的台湾中国患者。在所检查的 STAT6 SNPs 中，A 等位基因的剂量效应和 rs1059513 的等位基因频率与感染 HCV-1 的患者的 SVR 呈负相关（分别为 P=0.0179 和 P=0.0235）。这一效应在感染 HCV-2 的患者中并未观察到。包含 2、3 和 4 个 SNP（rs1059513、rs703817、rs324015 和 rs3024974）的 GG、GGG 和 GGGC STAT6 单倍型与 SVR 相关，其存在可能增加感染 HCV-1 的患者成功治疗结果的可能性（分别为 P=0.0273、0.0352 和 0.0368）。此外，用于预测 SVR 的多变量逻辑回归模型表明，GGGC 单倍型携带者的存在相互影响 PEG-IFNα-RBV 治疗的结果。STAT6 SNPs 的存在及其与 SVR 的关联表明，STAT6 多态性可能影响标准治疗（SOC）下感染 HCV-1 的患者的治疗结果。
