Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia.
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.
Kuniholm
Mark H
MH
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. mark.kuniholm@einstein.yu.edu
Kovacs
Andrea
A
Gao
Xiaojiang
X
Xue
Xiaonan
X
Marti
Darlene
D
Thio
Chloe L
CL
Peters
Marion G
MG
Terrault
Norah A
NA
Greenblatt
Ruth M
RM
Goedert
James J
JJ
Cohen
Mardge H
MH
Minkoff
Howard
H
Gange
Stephen J
SJ
Anastos
Kathryn
K
Fazzari
Melissa
M
Harris
Tiffany G
TG
Young
Mary A
MA
Strickler
Howard D
HD
Carrington
Mary
M
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*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D012367:RNA, Viral