The Associations of HLA-A*02:01 and DRB1*11:01 with Hepatitis C Virus Spontaneous Clearance Are Independent of IL28B in the Chinese Population

Abstract

Spontaneous clearance of hepatitis C virus (HCV) occurs in 10–40% of the infections. Specific human leukocyte antigen (HLA) alleles have been identified in associating with HCV clearance. However, data on the association of HLA with the spontaneous clearance of HCV are scarce in the Chinese population. In the current study we studied the HLA class I and class II genes in 231 Chinese voluntary blood donors who had cleared HCV infection spontaneously compared to 429 subjects with chronic HCV infections. We also studied their IL28B SNP (rs8099917) genotype, since a number of investigators have found a strong association of IL28B with spontaneous or treatment induced HCV clearance. We found that HLA-A*02:01 and DQB1*05:02 distributed differently between the two groups after Bonferroni correction (odds ratio [OR] = 1.839, Pc = 0.024 and OR = 0.547, Pc = 0.016, respectively). Multivariate logistic regression analysis suggested that A*02:01 and DRB1*11:01 (OR = 1.798, P = 0.008 and OR = 1.921, P = 0.005, respectively) were associated with HCV spontaneous clearance, independent of age, gender and IL28B polymorphism. We concluded that in the Chinese population, HLA-A*02:01 and DRB1*11:01 might be associated with the host capacity to clear HCV independent of IL28B, which suggesting that the innate and adaptive immune responses both play an important role in the control of HCV.

Association of HLA‐DQB1*03:01 and DRB1*11:01 with spontaneous clearance of hepatitis C virus in Chinese Li ethnicity, an ethnic group genetically distinct from Chinese Han ethnicity and infected with unique HCV subtype

“…HLA‐A, B, C, DPB1, DQB1, and DRB1 alleles of the studied subjects were genotyped and compared with that of Chinese Han ethnicity. The data of HLA genotyping for the Han ethnicity (n = 660) have been reported in our previous study . Among the 19 HLA class I alleles (>5% frequencies in either group) shown in Figure A, the frequencies of 7 alleles were significantly higher in the Chinese Li than Han subjects who were HCV‐seropositive ( Pc < .05), including A*11:01, A*33:03, B*13:01, B*40:02, B*58:01, C*03:02, and C*03:04.…”

“…However, such association was not found in the current study, which can be simply explained by the very low prevalence of A*02:01 in the Li population. Besides, although A*02:03 and A*02:07 were more prevalent in Li people (8.7% and 9.8%, respectively), they do not associate with HCV spontaneous clearance, which is consistent with that in Chinese Han population . These results emphasized the importance of high‐resolution HLA genotyping, which provide more detailed information to predict viral outcome and unravel the underlying mechanism.…”

“…Any ambiguous results were applied to additional exon sequencing. IFNL3 SNP (rs8099917) was genotyped by PCR and Sanger sequencing also as previously described …”

“…Notably, HLA‐A*02:01 was ten‐fold more prevalent in Han than Li people (7.4% vs 0.7%). In our previous study, A*02:01 associated with HCV clearance in Chinese Han population . However, such association was not found in the current study, which can be simply explained by the very low prevalence of A*02:01 in the Li population.…”

“…HLA class I (A, B, C) and class II (DPB1, DQB1, DRB1) alleles were determined by polymerase chain reaction–sequencing based typing (PCR‐SBT) as previously described . In brief, genomic DNAs from each study subject were extracted from 1 mL whole blood in automated MagNA Pure LC 2.0 instrument (Roche Diagnostics, Indianapolis, IN) using MagNA Pure LC DNA Isolation Kit (Roche Diagnostics), following the manufacturer's instruction.…”