title: Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia.
abstract: Studies of human leukocyte antigen (HLA) alleles and their relation with hepatitis C virus (HCV) viremia have had conflicting results. However, these studies have varied in size and methods, and few large studies assessed HLA class I alleles. Only one study conducted high-resolution class I genotyping. The current investigation therefore involved high-resolution HLA class I and II genotyping of a large multiracial cohort of U.S. women with a high prevalence of HCV and HIV. Our primary analyses evaluated associations between 12 HLA alleles identified through a critical review of the literature and HCV viremia in 758 HCV-seropositive women. Other alleles with >5% prevalence were also assessed; previously unreported associations were corrected for multiple comparisons. DRB1*0101 (prevalence ratio [PR] = 1.7; 95% confidence interval [CI] = 1.1-2.6), B*5701 (PR=2.0; 95% CI = 1.0-3.1), B*5703 (PR = 1.7; 95% CI = 1.0-2.5), and Cw*0102 (PR = 1.9; 95% CI = 1.0-3.0) were associated with the absence of HCV RNA (i.e., HCV clearance), whereas DRB1*0301 (PR = 0.4; 95% CI = 0.2-0.7) was associated with HCV RNA positivity. DQB1*0301 was also associated with the absence of HCV RNA but only among HIV-seronegative women (PR = 3.4; 95% CI = 1.2-11.8). Each of these associations was among those predicted. We additionally studied the relation of HLA alleles with HCV infection (serostatus) in women at high risk of HCV from injection drug use (N = 838), but no significant relationships were observed.
  
  
  CONCLUSIONS
  HLA genotype influences the host capacity to clear HCV viremia. The specific HLA associations observed in the current study are unlikely to be due to chance because they were a priori hypothesized.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. mark.kuniholm@einstein.yu.edu
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kuniholm
authors.forename: Andrea
authors.initials: A
authors.lastname: Kovacs
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.forename: Darlene
authors.initials: D
authors.lastname: Marti
authors.forename: Chloe L
authors.initials: CL
authors.lastname: Thio
authors.forename: Marion G
authors.initials: MG
authors.lastname: Peters
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: Mardge H
authors.initials: MH
authors.lastname: Cohen
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Melissa
authors.initials: M
authors.lastname: Fazzari
authors.forename: Tiffany G
authors.initials: TG
authors.lastname: Harris
authors.forename: Mary A
authors.initials: MA
authors.lastname: Young
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology / Q000821:virology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000821:virology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D015819:Substance Abuse, Intravenous; D014766:Viremia / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012367:RNA, Viral