Abstract
Human leukocyte antigen (HLA) class II molecule influences host antigen presentation and anti-viral immune response. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) within HLA class II gene were associated with different clinical outcomes of hepatitis C virus (HCV) infection. Three HLA class II SNPs (rs3077, rs2395309 and rs2856718) were genotyped by TaqMan assay among Chinese population, including 350 persistent HCV infection patients, 194 spontaneous viral clearance subjects and 973 HCV-uninfected control subjects. After logistic regression analysis, the results indicated that the rs2856718 TC genotype was significantly associated with the protective effect of the HCV natural susceptibility (adjusted OR: 0.712, 95% CI: 0.554–0.914) when compared with reference TT genotype, and this remained significant after false discovery rate (FDR) correction (p = 0.024). Moreover, the protective effect of rs2856718 was observed in dominant genetic models (adjusted OR: 0.726, 95% CI: 0.574–0.920), and this remained significant after FDR correction (p = 0.024). In stratified analysis, a significant decreased risk was found in rs2856718C allele in the male subgroup (adjusted OR: 0.778, 95% CI: 0.627–0.966) and hemodialysis subgroup (adjusted OR: 0.713, 95% CI: 0.552–0.921). Our results indicated that the genetic variations of rs2856718 within the HLA-DQ gene are associated with the natural susceptibility to HCV infection among the Chinese population.
Highlights
Hepatitis C virus (HCV) is estimated to infect 185 million people worldwide, which poses an increasingly severe global health burden [1]
Virus (HBV) infection, response to HBV vaccination and interferon therapy worldwide [13,15]. It is currently not known whether Human leukocyte antigen (HLA)-DP: rs3077, rs2395309 and HLA-DQ: rs2856718, which are frequently reported to be related to HBV infection among Japanese, Korean and many other ethnic groups, have an association with the outcomes of hepatitis C virus (HCV) infection among Chinese population
In light of the potential influence of HLA class II polymorphisms on the immune response in HCV infection, we examined the relationships of the three single nucleotide polymorphisms (SNPs) and HCV infection outcomes among the Chinese Han population
Summary
Hepatitis C virus (HCV) is estimated to infect 185 million people worldwide, which poses an increasingly severe global health burden [1]. Many HLA class II alleles were considered to correlate with the natural susceptibility, viral persistence/clearance, liver cirrhosis, progressive liver damage, viral load, response to interferon therapy, vertical transmission, and extra-hepatic manifestations of HCV infection in global populations [13]. Many HLA class II alleles were considered as candidate genetic markers in hepatitis B virus (HBV) infection, response to HBV vaccination and interferon therapy worldwide [13,15] It is currently not known whether HLA-DP: rs3077, rs2395309 and HLA-DQ: rs2856718, which are frequently reported to be related to HBV infection among Japanese, Korean and many other ethnic groups, have an association with the outcomes of HCV infection among Chinese population. We found the genetic variations of rs2856718 are associated with the natural susceptibility to HCV infection in the Chinese population
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