| Background:Hepatitis C virus (HCV) can cause human hepatitis C. Approximately 20% of individuals spontaneously clear acute HCV infection, while the remaining may proceed to chronicity and then may develop into liver fibrosis, cirrhosis or hepatocellular carcinoma. Thus, the roles which host immune system genetic factors played in HCV clearance or persistent infection are one research hotspot. As an important part of the immune system of host, human leukocyte antigen (HLA) and killer cell immunoglobulin receptor (KIR) gene system, play a key role in immune response. HLA genes determined the type and effectiveness of viral epitope present in the immune response, and determine the effective response to specific virus. HLA and KIR which is also play an important role in infection defense work independently or synergisticly affect the pathogenesis. In addition, CD6 plays an important role in the process of activation and proliferation of T cells, and its genetic polymorphisms may indirectly influence the role of T cells, resulting in different processes of virus infection.The aim of this study was to analyze the association between the HLA/KIR gene and their specific combination, and CD6 gene polymorphism and the chronic infection of HCV, and provide some basic data for the prevention and treatment of hepatitis C.Methods:There are two parts in this study. In the first part, to investigate the association between HLA/KIR gene polymorphisms and HCV chronic infection,301 HCV chronical infected patients and 239 healthy controls of Han population in Yunnan province were collected. Next-generation sequencing (NGS) technology was used to perform high resolution genotyping of HLA-A,-B,-C; PCR-sequence specific primer (PCR-SSP) proceedure was uesd to genotype KIR genes. Pypop software was used to calculate the frequency of HLA genes, and constructe HLA A-B, A-C, C-B, A-C-B haplotypes. Hardy-Weinberg equilibrium and Ewens-Watterson neutral test were performed on each locus. The distribution of HLA-A, B, C alleles and haplotypes, the phenotypes, genotypes and haplotypes of KIR gene, and HLA-KIR gene specific combinations were compared between case and control groups to investigate the association between HLA/KIR gene system and HCV chronic infection. In the second part, to investigate the association between CD6 gene single nucleotide ploymorphism and HCV chronic infection,434 HCV chronic infected patients and 444 healthy controls of Han population in Yunnan province were chosen. TaqMan methods was used to genotype three SNPs (rs17824933, rs12360861, rs11230563) in CD6 gene. The distribution of allele frequencies, haplotypes between case and control group were compared to evaluate the association of CD6 gene polymorphisms with chronic HCV infection.Results:(1) There are 31 types of HLA-A alleles,47 types of HLA-B alleles, and 33 types of HLA-C alleles were detected in HCV chronic infection group in Yunnan province; 27 types of HLA-A alleles,54 types of HLA-B alleles,31 types of HLA-C alleles were detected in normal healthy individuals. (2) The frequency of HLA-B*13:01(P<0.001) and C*08:04 (P=0.001) is significantly lower in case group than that in control group. (3) The distribution of HLA haplotypes A*11:01-B*15:01(P=0.001), A*24:02-B*13:01(P=0.001), A*11:01:C*08:01(P=0.001), A*24:02:C*04:01(P<0.001), and B*13:01-C*03:04(P=0.001) are significant different between case and control groups. (4) The frequency of KIR 2DL2 gene appearance (f=0.243, KLF=0.130) in case group is significantly higher compared to control group (f=0.163, KLF=0.085)(P=0.024). (5) The frequency of activating KIR+HLA pair 2DS1+HLA-C2 in case group was significantly lower than control group (P=0.028). (6) The frequency of genotype and allele frequencies of SNP-rs17824933, rs12360861 and rs11230563 in CD6 gene showed no significant difference (P>0.05) between case and control group, and the frequency of haplotypes constructed by SNP-rs 17824933, rs12360861 and rs11230563 were not significantly different between case group and control group (P>0.05).Conclusion:(1) HLA-B*13:01 and C*08:04 may be protective alleles for HCV chronical infection in Yunnan Han population; A*11:01-C*08:01 might be susceptible haplotype and A* 11:01-B* 15:01, A*24:02-B*13:01, A*24:02-C*04:01, B*13:01-C*03:04 might be protective haplotype for HCV chronic infection in Yunnan Han population. (2) The polymorphisms of KIR gene were associated with HCV chronic infection:2DL2 gene may be susceptible factor for HCV chronic infection. (3) Activating KIR+HLA pair 2DS1+HLA-C2 may be protective factor for chronically infected with HCV in Yunnan Han population. (4) There are no significant differences of SNPs frequency in CD6 gene between HCV chronic infection group and healthy control group observed in this study. SNP-rs17824933, rsl2360861 and rs11230563 of CD6 gene may not susceptibility or protection factors for HCV chronic infection in Yunnan Han population. |
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