Association of polymorphisms in HLA antigen presentation-related genes with the outcomes of HCV infection

PLoS One. 2015 Apr 13;10(4):e0123513. doi: 10.1371/journal.pone.0123513. eCollection 2015.

Abstract

Antigen-presentation genes play a vital role in the pathogenesis of HCV infection. However, the relationship of variants of these genes with spontaneous outcomes of HCV infection has not been fully investigated. To explore novel loci in the Chinese population, 34 tagging-SNPs in 9 candidate genes were genotyped for their associations with the outcomes of HCV infection. The distributions of different genotypes and haplotypes were compared among 773 HCV-negative controls, 246 subjects with HCV natural clearance, and 218 HCV persistent carriers recruited from hemodialysis patients and intravenous drug users. Our study implicated that TAP2, HLA-DOA, HLA-DOB, and tapasin loci were novel candidate regions for susceptibility to HCV infection and viral clearance in the Chinese population. Logistic regression analyses showed that TAP2 rs1800454 A (OR = 1.48, P = 0.002) and HLA-DOB rs2071469 G (OR = 1.23, P = 0.048) were significantly associated with increased susceptibility to establishment of HCV infection. However, high-risk behavior exposure and age were stronger predictors of HCV infection. Mutation of tapasin rs9277972 T (OR = 1.57, P =0.043) increased the risk of HCV chronicity, and HLA-DOA rs3128935 C (OR = 0.62, P = 0.019) increased the chance of viral resolution. With regards to the effect of rs3128925, interactions were found with high-risk behavior (P = 0.013) and age (P = 0.035). The risk effect of rs3128925 T for persistent HCV infection was higher in injecting drug users (vs. dialysis patients) and in subjects ≥ 40 years old (vs. < 40 years old).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters / genetics
  • Adult
  • Alleles
  • Area Under Curve
  • Asians / genetics
  • China
  • Drug Users
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA Antigens / genetics*
  • HLA-D Antigens / genetics
  • Haplotypes
  • Hepacivirus
  • Hepatitis C / genetics*
  • Humans
  • Logistic Models
  • Male
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • ROC Curve
  • Renal Dialysis

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • HLA Antigens
  • HLA-D Antigens
  • HLA-DO antigens
  • Membrane Transport Proteins
  • tapasin
  • TAP2 protein, human

Grant support

This work was supported by the National Natural Science Foundation of China (Grant No.81102164 to JS, No.81102165 to JS, and No.81273146 to YZ), http://www.nsfc.gov.cn/. The work was also supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) (to Nanjing Medical University, major of public health and preventive medicine), http://english.jsjyt.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.