Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan.
Gut. 2011 Feb;60(2):261-7. doi: 10.1136/gut.2010.223495. Epub 2010 Nov 10.
A number of recent studies have shown that human polymorphisms near the IL28B type III interferon (IFNλ) gene influence the response to peg-interferon plus ribavirin combination therapy for infection with chronic hepatitis C virus (HCV). Viral polymorphisms, including substitutions within the HCV core and NS5A proteins, have also been shown to influence treatment outcome, but it is not known whether these factors act independently of the IL28B polymorphism or if they reflect the same or a different underlying mechanism. Multiple logistic regression was used to determine whether host and viral polymorphisms independently predict sustained virological response (SVR).
Two single nucleotide polymorphisms were genotyped in the IL28B locus (rs12979860 and rs8099917) from 817 patients with chronic HCV infection, and substitutions at amino acids 70 and 91 of the HCV core protein and within the NS5A interferon sensitivity-determining region (ISDR) were analysed.
It was found that independent predictors of an SVR included IL28B rs12979860 CC genotype (OR=4.98; p=4.00E-08), core amino acid 70 substitutions (OR=0.53; p=0.016), age and baseline viral load. For non-virological response, the IL28B rs12979860 CT/TT genotype (OR=0.23; p=1.96E-8) and age were independent predictors. IL28B rs12979860 genotype (p=1.4E-8), core amino acid 70 substitutions (p=0.0013), ISDR substitutions (p=0.0019), baseline viral load, γ-glutamyltranspeptidase, alanine aminotransferase and platelet count were independent predictors for change in viral load by week 4 of treatment.
IL28B polymorphisms and HCV core amino acid 70 substitutions contribute independently to an SVR to peg-interferon plus ribavirin combination therapy.
近期多项研究表明，人类白细胞介素 28B 型 III 干扰素（IFNλ）基因附近的多态性影响聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎病毒（HCV）感染的应答。病毒多态性，包括 HCV 核心和 NS5A 蛋白内的替换，也已被证明影响治疗结果，但尚不清楚这些因素是否独立于 IL28B 多态性起作用，或者它们是否反映了相同或不同的潜在机制。多变量逻辑回归用于确定宿主和病毒多态性是否独立预测持续病毒学应答（SVR）。
对 817 例慢性 HCV 感染患者的 IL28B 基因座（rs12979860 和 rs8099917）进行了两种单核苷酸多态性基因分型，并分析了 HCV 核心蛋白氨基酸 70 和 91 的替换以及 NS5A 干扰素敏感性决定区（ISDR）内的替换。
发现 SVR 的独立预测因素包括 IL28B rs12979860 CC 基因型（OR=4.98；p=4.00E-08）、核心氨基酸 70 替换（OR=0.53；p=0.016）、年龄和基线病毒载量。对于非病毒学应答，IL28B rs12979860 CT/TT 基因型（OR=0.23；p=1.96E-8）和年龄是独立的预测因素。IL28B rs12979860 基因型（p=1.4E-8）、核心氨基酸 70 替换（p=0.0013）、ISDR 替换（p=0.0019）、基线病毒载量、γ-谷氨酰转肽酶、丙氨酸氨基转移酶和血小板计数是治疗第 4 周时病毒载量变化的独立预测因素。
IL28B 多态性和 HCV 核心氨基酸 70 替换独立于聚乙二醇干扰素联合利巴韦林治疗的 SVR。
