Abstract
BackgroundsThe association of human leukocyte antigen (HLA) genes with the outcome of hepatitis C virus (HCV) infection may be modified by ethnic and geographical differences.ResultsHLA-A, -C, -DRB1 and -DQB1 genotyping were performed in a Midwestern American cohort of 105 HCV infected subjects among which 49 cleared HCV infection and 56 had persistent viral infection. A new protective association of HLA-Cw*05 to HCV infection of all ethnic populations was identified (OR = 0.12, 95% CI = 0.01–0.97, P = 0.03). It was surprising that HLA-A*02 (P for interaction = 0.02) and HLA-DRB1*12 (P for interaction = 0.05) showed statistical interaction with race indicating opposite associations in Caucasians (OR = 2.74 for A*02 and 2.15 for DRB1*12) and non-Caucasians (OR = 0.41 for A*02 and 0.15 for DRB1*12). In addition, HLA-DRB1*01 (OR = 0.26), DQB1*05 (OR = 0.23) and the haplotype DRB1*01-DQB1*05 (OR = 0.19) showed strong associations with viral clearance in Caucasians. The protective associations of A*03 (OR = 0.20) and DQB1*03 (OR = 0.20) were exclusive to non-Caucasians. In contrast, DQB1*02 (OR = 2.56, 95% CI = 1.15–7.71, P = 0.02) and the haplotype DRB1*07-DQB1*02 (OR = 5.25, 95% CI = 1.04–26.6, P = 0.03) were risk markers in Caucasians.ConclusionThe associations of HLA-A*02 and HLA-DRB1*12 with HCV infection are opposite with different races. HLA-A*03, Cw*05, DRB1*01, DQB1*03 and DQB1*05 are associated with viral clearance while HLA-DRB1*07 and DQB1*02 are risk markers for viral persistence of HCV infection in Midwestern Americans. These results reveal ethnically and geographically different distribution of HLA-genes which are associated with the outcome of HCV infection.
Highlights
Cellular immunity is believed to play a central role in the host control of hepatitis C virus (HCV) infection [3,4,5,6,7,8,9,10,11,12]
To elicit an adaptive cellular immune response, HCV antigens are processed into peptides that bind human leukocyte antigen (HLA) molecules
We show that HLA association with the outcome of early HCV infection is significantly different among different races
Summary
Subjects with HCV infection One hundred and five subjects who were exposed to HCV in the Chicago area were divided into two groups: group 1 included 56 patients with persistent HCV infection and group 2 included 49 subjects with spontaneous viral clearance (Table 1). A strong protective association of Cw*01 to HCV clearance has been reported in European and Northeastern American Caucasians in Baltimore [15,17]. Our data show that the allele frequencies of Cw*01 in chronic infection and viral clearance is 1.79% versus 4.08%, respectively, but this difference is not statistically significant (Table 2). The associations of HLA-class II alleles with HCV infection The protective associations of DRB1*0101 and DQB1*0501 have been documented in Northeastern American Caucasians in Baltimore whereas in African Americans, viral clearance is mainly associated with DQB1*0301 [18]. Logistic regression analysis demonstrated that there is a strong protective association with the haplotype DRB1*01-DQB1*05 (OR = 0.20) This is statistically significant in Caucasians only (OR = 0.19). It appears that risk associations of especially class II alleles are less common in non-Caucasians (Table 4)
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