Hospital Universitari de Tarragona Joan XXIII, IISPV, Universitat Rovira i Virgili, Tarragona, Spain.
PLoS One. 2012;7(11):e47725. doi: 10.1371/journal.pone.0047725. Epub 2012 Nov 2.
This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients.
The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses.
As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p = 0.01) remained significant.
In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism.
这是一项安全性和疗效的遗传药理学研究，对之前进行的一项随机试验进行了分析，该试验比较了聚乙二醇干扰素 α（pegIFNα）2a 与 2b 联合利巴韦林治疗 HCV-HIV 合并感染患者 48 周的疗效，这些患者的治疗方法是治疗丙型肝炎病毒感染。
研究组由 99 名患者（疗效遗传药理学亚研究）和 114 名患者（安全性遗传药理学亚研究）组成。评估了以下候选基因 IL28B、IL6、IL10、TNFα、IFNγ、CCL5、MxA、OAS1、SOCS3、CTLA4 和 ITPA 的多态性。使用Sequenom iPLEX-Gold （一种单碱基延伸聚合酶链反应）进行基因分型。疗效终点评估包括：快速、早期和持续病毒学应答（RVR、EVR 和 SVR，分别）。安全性终点评估包括：贫血、中性粒细胞减少、血小板减少、流感样综合征、胃肠道紊乱和抑郁。使用卡方检验、学生 T 检验、Mann-Whitney U 检验和逻辑回归进行统计分析。
就疗效而言，IL28B 和 CTLA4 基因多态性与 RVR 相关（两者比较 p<0.05）。然而，只有 IL28B 基因的多态性与 SVR 相关（p=0.004）。在多变量分析中，唯一与 SVR 相关的基因是 IL28B（OR 2.61，95%CI 1.2-5.6，p=0.01）。关于安全性，流感样综合征或抑郁与所研究的遗传变异之间没有显著关联。胃肠道紊乱与 ITPA 基因多态性相关（p=0.04）。贫血与 OAS1 和 CTLA4 基因多态性相关（p=0.049 和 p=0.045），中性粒细胞减少和血小板减少与 SOCS3 基因多态性相关（p=0.02 和 p=0.002）。在多变量分析中，SOCS3 基因多态性与中性粒细胞减少（OR 0.26，95%CI 0.09-0.75，p=0.01）和血小板减少（OR 0.07，95%CI 0.008-0.57，p=0.01）的相关性仍然显著。
在接受聚乙二醇干扰素 α和利巴韦林治疗的 HCV-HIV 合并感染患者中，SVR 与 IL28B rs8099917 多态性相关。HCV 治疗诱导的中性粒细胞减少和血小板减少与 SOCS3 rs4969170 多态性相关。
