Ea Rashwan, Aa Ghazy, Ag El-Sheredy, Ma Abdelnaby
Department of Immunology & Allergy, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Department of Microbiology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Egypt J Immunol. 2015 Jun;22(2):57-68.
HCV infection is a serious public health problem and a leading cause of chronic liver disease. It affects nearly 3% of the world's population with an associated high mortality. Egypt has the highest prevalence of HCV infection in the world (estimated at >10%). Peg-IFN-α and RBV are the most widely used therapy for HCV. Unfortunately, the rate of SVR is around 50%. In addition, it is expensive and associated with considerable adverse effects. Thus selection of patients with the highest probability of response is essential for clinical practice. It is suggested that some SNPs near IL- 28B gene could be important genetic predictors of treatment response among HCV. Our study aimed to study two different Interleukin 28B polymorphisms (rs12979860 and rs8099917) and T-helper 1 response in HCV infected patients. The current study was conducted on 60 chronic HCV infected patients and 20 healthy volunteers. Grouping of patients was done according to response to treatment into naïve, responder and non-responder HCV patients. Assessment of liver functions' tests, measuring HCV RNA levels using real time PCR, measurement of interferon-γ levels using ELISA and genotyping of IL-28 rs2979860 and rs8099917 SNPs using 5' nuclease assay were done. Concerning IL-28B rs12979860; TT genotype was highly expressed in non-responder HCV patients but statistically insignificant. While for IL-28B rs8099917, there was lack of association between its different genotypes and SVR. IFN- level was significantly increased among responder HCV patients carrying IL28B rs12979860 TT genotype and/or IL28B rs8099917 GG allele. There was statistically significant positive correlation between L28B rs8099917 GG genotype and HCV-RNA. In conclusion, IL-28B rs12979860 SNP could be used as an independent predictor for treatment response among HCV patients.
丙型肝炎病毒（HCV）感染是一个严重的公共卫生问题，也是慢性肝病的主要病因。它影响着全球近3%的人口，死亡率较高。埃及是全球HCV感染率最高的国家（估计超过10%）。聚乙二醇化干扰素-α（Peg-IFN-α）和利巴韦林（RBV）是治疗HCV最广泛使用的疗法。不幸的是，持续病毒学应答（SVR）率约为50%。此外，该疗法费用高昂且伴有相当多的不良反应。因此，选择最有可能产生应答的患者对于临床实践至关重要。有人认为，白细胞介素-28B（IL-28B）基因附近的一些单核苷酸多态性（SNP）可能是HCV治疗应答的重要遗传预测指标。我们的研究旨在研究HCV感染患者中两种不同的白细胞介素28B多态性（rs12979860和rs8099917）以及辅助性T细胞1应答。本研究对60例慢性HCV感染患者和20名健康志愿者进行。根据治疗反应将患者分为初治、应答和无应答的HCV患者组。进行了肝功能检查评估、使用实时聚合酶链反应（PCR）测量HCV RNA水平、使用酶联免疫吸附测定（ELISA）测量干扰素-γ水平以及使用5'核酸酶测定法对IL-28 rs2979860和rs8099917单核苷酸多态性进行基因分型。关于IL-28B rs12979860；TT基因型在无应答的HCV患者中高表达，但无统计学意义。而对于IL-28B rs8099917，其不同基因型与SVR之间缺乏关联。携带IL28B rs12979860 TT基因型和/或IL28B rs8099917 GG等位基因的应答HCV患者中，干扰素-γ水平显著升高。L28B rs8099917 GG基因型与HCV-RNA之间存在统计学显著的正相关。总之，IL-28B rs12979860单核苷酸多态性可作为HCV患者治疗应答的独立预测指标。
