title: Genetic variants in antigen presentation-related genes influence susceptibility to hepatitis C virus and viral clearance: a case control study.
abstract: BACKGROUND
  Genes related to antigen presentation pathway, which are in the non-classical class-II region of human leukocyte antigen (HLA), play a vital role during the infection of hepatitis C virus (HCV).
  
  
  METHODS
  The current study determined the genotypes of 34 tagging-SNPs (single nucleotide polymorphisms) from 9 candidate genes (HLA-DMA, HLA-DMB, HLA-DOA, HLA-DOB, TAP1, TAP2, LMP2, LMP7, and tapasin) in a Chinese population of paid blood donors with high risk of HCV infection. The distributions of those SNPs were compared among the 1207 former paid blood donors with different HCV infection outcomes.
  
  
  RESULTS
  HLA-DMA rs1063478 and HLA-DOA rs2284191 were independent factors of acquiring HCV infection. Carrying three favorable alleles of rs1063478-T and rs2284191-G offered the highest protective effect (odds ratio = 0.46, 95% confidence intervals = 0.27-0.78). HLA-DOB rs7383287 and LMP2 rs17587 were independent factors of infection chronicity. Subjects carrying two favorable alleles of rs7383287-G and rs17587-A had a decreased risk of HCV chronicity (odds ratio = 0.42, 95% confidence intervals = 0.26-0.66). The interaction analysis showed that experience of plasma donation interacted with the combined effects of rs1063478 and rs2284191 for HCV susceptibility, and the experience of whole blood donation interacted with the association of rs7383287 with HCV clearance.
  
  
  CONCLUSIONS
  Our results suggested that genetic variants in antigen presentation pathway had influence on susceptibility to HCV infection and viral clearance. HLA-DMA rs1063478, HLA-DOA rs2284191, and HLA-DOB rs7383287 were identified as novel loci in Chinese population that were involved in HCV infection.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. hp19880310@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, the People's Hospital of Jiangsu Province, Nanjing, 210029, China. lilid1973@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. luxiaomei1981@sina.com.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. jsqdzyy@126.com.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, the Jurong People's Hospital, Jurong, 212400, China. chb2180@126.com.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Practice, Kangda College, Nanjing Medical University, Nanjing, 210029, China. wangjie.nj@gmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, Medical Institute of Nanjing Army, Nanjing, 210002, China. zhangyun111@sina.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. sujing@njmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. rongbinyu@njmu.edu.cn.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Yu
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D000483:Alleles; D017951:Antigen Presentation / Q000235:genetics* / Q000276:immunology; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D003546:Cysteine Endopeptidases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006681:HLA-D Antigens / Q000235:genetics; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D006681:HLA-D Antigens; C073119:TAP1 protein, human; C071313:LMP-2 protein; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex