Azam Sikandar, Manzoor Sobia, Imran Muhammad, Ashraf Javed, Ashraf Sarah, Resham Saleha, Ghani Eijaz
1 Atta-ur-Rehman School of Applied Bio-Sciences, Department of Healthcare Biotechnology, National University of Sciences and Technology , Islamabad, Pakistan .
Viral Immunol. 2015 May;28(4):222-8. doi: 10.1089/vim.2014.0111. Epub 2015 Mar 23.
Hepatitis C virus (HCV) pathogenesis and treatment outcomes are multifactorial phenomena involving both viral and host factors. This study was designed to determine the role of tumor necrosis factor-related apoptosis-inducing ligand receptor 1(TRAIL-R1) and interferon gamma (IFN-γ) genetic mutations in susceptibility and response to interferon-based therapy of hepatitis C virus (HCV) infection. The detection of TRAIL-R1 rs4242392 and IFN-γ rs2069707 single nucleotide polymorphisms was completed in 118 chronic HCV patients and 96 healthy controls by allele-specific polymerase chain reaction and restriction fragment length polymorphisms polymerase chain reaction. Patients were further categorized into sustained virological responder (SVR) and nonresponder (NR) groups on the basis of their response to interferon-based therapy for HCV infection. Real-time PCR was used for HCV quantification. HCV genotyping was performed by Ohno's method. The results demonstrated that the distribution of the TRAIL-R1 rs4242392TT genotype was significantly higher in the SVR group (78%) compared to the NR group (36%). It showed that chronic HCV patients possessing the TRAIL-R1 rs4242392TT genotype are better responders to interferon-based therapy (p<0.05). The prevalence of the TRAIL-R1 rs4242392TT genotype in healthy controls and chronic HCV patients was 56% and 65% respectively. It indicated that there is the TRAIL-R1 rs4242392 genetic variation plays no role in the spontaneous clearance of HCV infection (p>0.05). The distribution of IFN-γ rs2069707 was the opposite to TRAIL-R1 rs4242392 prevalence, that is, there was high distribution of the IFN-γ rs2069707GG genotype in patients and healthy controls (p<0.05), while the prevalence of IFN-γ rs2069707GG in SVR and NR groups was comparable (p>0.05). In conclusion, genetic variation of TRAIL-R1 rs4242392 is linked with response to interferon-based therapy for HCV infection, and genetic variation IFN-γ rs2069707 is associated with natural clearance of HCV infection.
丙型肝炎病毒（HCV）的发病机制和治疗结果是涉及病毒和宿主因素的多因素现象。本研究旨在确定肿瘤坏死因子相关凋亡诱导配体受体1（TRAIL-R1）和干扰素γ（IFN-γ）基因突变在丙型肝炎病毒（HCV）感染对基于干扰素治疗的易感性和反应中的作用。通过等位基因特异性聚合酶链反应和限制性片段长度多态性聚合酶链反应，在118例慢性HCV患者和96例健康对照中完成了TRAIL-R1 rs4242392和IFN-γ rs2069707单核苷酸多态性的检测。根据患者对HCV感染基于干扰素治疗的反应，进一步将其分为持续病毒学应答者（SVR）和无应答者（NR）组。采用实时PCR进行HCV定量。通过Ohno方法进行HCV基因分型。结果表明，与NR组（36%）相比，SVR组（78%）中TRAIL-R1 rs4242392TT基因型的分布显著更高。这表明具有TRAIL-R1 rs4242392TT基因型的慢性HCV患者对基于干扰素的治疗反应更好（p<0.05）。健康对照和慢性HCV患者中TRAIL-R1 rs4242392TT基因型的患病率分别为56%和65%。这表明TRAIL-R1 rs4242392基因变异在HCV感染的自发清除中不起作用（p>0.05）。IFN-γ rs2069707的分布与TRAIL-R1 rs4242392的患病率相反，即患者和健康对照中IFN-γ rs2069707GG基因型的分布较高（p<0.05），而SVR组和NR组中IFN-γ rs2069707GG的患病率相当（p>0.05）。总之，TRAIL-R1 rs4242392的基因变异与HCV感染基于干扰素治疗的反应相关，而IFN-γ rs2069707的基因变异与HCV感染的自然清除相关。
