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首页> 外文期刊>International journal of infectious diseases : >Polymorphism of the IL28B gene (rs8099917, rs12979860) and virological response of Pakistani hepatitis C virus genotype 3 patients to pegylated interferon therapy
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Polymorphism of the IL28B gene (rs8099917, rs12979860) and virological response of Pakistani hepatitis C virus genotype 3 patients to pegylated interferon therapy

机译：IL28B基因的多态性（rs8099917，rs12979860）和巴基斯坦丙型肝炎病毒基因型3患者对聚乙二醇干扰素治疗的病毒学应答

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Background: The gold standard treatment for chronic hepatitis C virus (HCV) infection is pegylated interferon (PEG-IFN) in combination with ribavirin. Most patients treated with PEG-IFN achieve a sustained virological response (SVR). However host genetic factors play a vital role in the spontaneous and treatment-induced clearance of HCV infection from these infected patients. In the current study, polymorphisms of IL28B (rs8099917 and rs12979860) were analyzed and their association with the virological response to PEG-IFN alpha treatment was determined. Methods: One hundred and fifty HCV genotype 3 patients were assessed to study the correlation of IL28B with a therapeutic regimen of PEG-IFN alpha plus ribavirin. Twenty patients were excluded due to a refusal to participate in the study and 25 patients failed to meet the inclusion criteria. Of the 105 patients recruited, 49 (46.7%) were male and 56 (53.3%) were female. In order to determine single nucleotide polymorphisms of rs8099917 and rs12979860, the sample was amplified by PCR and then IL28B typing was carried out by restriction fragment length polymorphism (RFLP) followed by standard sequencing. Results: We found three types of genotype in rs8099917 of IL28B: wild-type TT in 60.0% of patients, heterozygous GT minor genotype in 36.2%, and GG in 3.8%. The frequency of the CC genotype of rs12979860 was 54.3%, CT was 37.1%, and TT was 8.6%. Overall, SVR was achieved in 68.6% of patients. A higher SVR was achieved for patients with the favorable genotype CC of rs12979860, with 84.2% as compared to 56.4% and 22.2% for minor genotype CT and TT, respectively (p=0.0001). We did not find a significant association for SVR to antiviral treatment in patients with genotype TT (rs8099917) (71.9%, p=0.36). The rapid virological response (RVR) rate was significantly higher in patients with major genotype TT (88.9%, p=0.04). These results show that IL28B polymorphism is highly associated with SVR to therapy in the Pakistani population infected with HCV genotype 3. Conclusions: HCV-infected patients carrying homozygous C/C have a higher chance of SVR. In addition, patients who carry T/T (rs8099917) have a higher chance of RVR.
机译：背景：慢性丙型肝炎病毒（HCV）感染的金标准疗法是聚乙二醇化干扰素（PEG-IFN）与利巴韦林联用。接受PEG-IFN治疗的大多数患者均达到持续的病毒学应答（SVR）。然而，宿主遗传因素在自发和治疗诱导的这些感染患者清除HCV感染中起着至关重要的作用。在本研究中，分析了IL28B的多态性（rs8099917和rs12979860），并确定了它们与对PEG-IFNα处理的病毒学应答的相关性。方法：对150例HCV基因3型患者进行评估，以研究IL28B与PEG-IFNα加利巴韦林治疗方案的相关性。 20名患者因拒绝参加研究而被排除在外，而25名患者未达到纳入标准。在招募的105位患者中，男性49位（46.7％），女性56位（53.3％）。为了确定rs8099917和rs12979860的单核苷酸多态性，通过PCR扩增样品，然后通过限制性片段长度多态性（RFLP）进行IL28B分型，然后进行标准测序。结果：我们在IL28B的rs8099917中发现了三种类型的基因型：60.0％的患者为野生型TT，36.2％的患者为杂合GT次要基因型，3.8％的为GG。 rs12979860的CC基因型频率为54.3％，CT为37.1％，TT为8.6％。总体而言，有68.6％的患者实现了SVR。具有良好基因型rs12979860的患者获得了更高的SVR，分别为84.2％和次要基因型CT和TT的56.4％和22.2％（p = 0.0001）。在基因型TT（rs8099917）的患者中，我们没有发现SVR与抗病毒治疗有显着相关性（71.9％，p = 0.36）。具有主要基因型TT的患者的快速病毒学应答（RVR）率显着更高（88.9％，p = 0.04）。这些结果表明，在感染了HCV基因型3的巴基斯坦人群中，IL28B多态性与SVR与治疗高度相关。结论：携带纯合C / C的HCV感染患者发生SVR的机会更高。此外，携带T / T（rs8099917）的患者发生RVR的机会更高。

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