The relationship between ITPA rs1127354 polymorphisms and efficacy of antiviral treatment in Northeast Chinese CHC patients.
The relationship between ITPA rs1127354 polymorphisms and efficacy of antiviral treatment in Northeast Chinese CHC patients.
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东北CHC患者ITPA rs1127354多态性与抗病毒治疗疗效的关系
DOI：
10.1097/md.0000000000007554
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发表时间：
2017-07
期刊：
影响因子：
1.6
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Liu Z;Wang S;Qi W;Wang X;Sun D;Wang H;Zhang Y;Li Z;Zhu L;Zhao P;Guo H;Zhou C;Wang J
摘要：这项前瞻性研究调查了 2 个肌苷三磷酸酶 (ITPA) 多态性（rs7270101 和 rs1127354）与中国丙型肝炎病毒 (HCV) 感染患者基于利巴韦林的抗病毒治疗疗效之间的关系。纳入2011年1月至2014年1月期间来自中国东北地区5个肝炎中心的906例诊断为慢性丙型肝炎并接受聚乙二醇干扰素（PEG-IFN）联合利巴韦林联合治疗的患者。根据感染HCV基因型将患者分为基因1型和非基因1型组。对所有患者进行 ITPA 单核苷酸多态性 (SNP) 基因分型。在治疗和随访期间监测利巴韦林诱导的溶血性贫血和病毒学反应（VR）。多变量回归分析用于分析持续病毒学应答（SVR）的预测因子。未检测到 IPTA rs7270101 变体。检测到 IPTA rs1127354 变异，并显示基因型 1 组和非基因型 1 组之间没有差异。 IPTA rs1127354 基因型 CC 与利巴韦林诱导的溶血性贫血的较高发生率相关。对于接受超过计划利巴韦林剂量 80% 的患者，rs1127354 变异和相关 ITPase 与更好的 SVR 相关。多变量分析显示，IPTA rs1127354非基因型CC、HCV基因型、基线HCV RNA水平<4 × 105 IU/mL、IL-28B rs12979860基因型CC和低肝纤维化是联合治疗期间SVR的独立预测因子。 IPTA rs1127354变异体及相关ITPase不仅与利巴韦林引起的溶血性贫血有关，而且直接影响中国HCV感染患者对PEG-IFN联合利巴韦林联合治疗的SVR。
Abstract This prospective study investigated the relationship between 2 inosine triphosphatase (ITPA) polymorphisms (rs7270101 and rs1127354) and the efficacy of ribavirin-based antiviral therapy in hepatitis C virus (HCV)-infected Chinese patients. A total of 906 patients diagnosed with chronic hepatitis C receiving pegylated interferon (PEG-IFN) plus ribavirin combination therapy between January 2011 and January 2014 from 5 hepatitis centers in Northeast China were enrolled. The patients were divided into genotype 1 and non-genotype 1 groups according to the genotype of infected HCV. ITPA single nucleotide polymorphism (SNP) genotyping was performed for all patients. Ribavirin-induced hemolytic anemia and virological response (VR) were monitored during treatment and follow-up. Multivariate regression analysis was used to analyze the predictors for sustained virological response (SVR). IPTA rs7270101 variants were not detected. IPTA rs1127354 variants were detected and showed no difference between the genotype 1 and non-genotype 1 groups. IPTA rs1127354 genotype CC was related to a higher incidence of ribavirin-induced hemolytic anemia. For patients who received >80% of the planned ribavirin dose, rs1127354 variants and related ITPase were related to better SVR. Multivariate analysis showed that IPTA rs1127354 non-genotype CC, HCV genotype, a baseline HCV RNA level <4 × 105 IU/mL, IL-28B rs12979860 genotype CC, and low liver fibrosis were independent predictors for SVR during the combination therapy. IPTA rs1127354 variants and related ITPase were not only related with ribavirin-induced hemolytic anemia but also directly affected the SVR to PEG-IFN plus ribavirin combination therapy in Chinese HCV-infected patients.