Association of human leukocyte antigen polymorphisms with occult hepatitis B virus infection in a Shaanxi Han population

Abstract

Background: Occult hepatitis B virus (HBV) infection (OBI) is defined as HBV DNA detection in serum or in the liver by sensitive diagnostic tests in HBV surface antigen (HBsAg) negative patients with or without serologic markers of previous HBV exposure. Because the human leukocyte antigen (HLA) system is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes were the key determinants of HBV persistence and clearance. The present study aimed to calculate the allelic frequency of HLA loci and investigate the association between HLA alleles and the outcome of OBI in Shaanxi Han population in the northwest of China.

Methods: We conducted a case-control study between 107 OBI subjects and 280 healthy control individuals from blood donors of Shaanxi Blood Center. Five HLA loci, including HLA-A,-B,-C,-DRB1 and -DQB1, were selected and further genotyped using a polymerase chain reaction sequence-based typing (SBT) method.

Results: Using the chi-squared test, we found that the allele frequencies of HLA-B*44:03 [odds ratios (OR) = 2.146, 95% confidence interval (CI) = 1.070-4.306, p = 0.028]; C*07:01 (OR = 4.693, CI = 1.822-12.086, p = 0.000); DQB1*02:02 (OR = 1.919, CI = 1.188-3.101, p = 0.007); and DRB1*07:01 (OR = 2.012, CI = 1.303-3.107, p = 0.001) were markedly higher in the OBI group compared to the healthy control group. The allele frequencies of HLA-DRB1*08:03 (OR = 0.395, CI = 0.152-1.027, p = 0.049); DRB1*15:01 (OR = 0.495, CI = 0.261-0.940, p = 0.029); and DQB1*06:02 (OR = 0.500, CI = 0.249-1.005, p = 0.048) were obviously lower in the OBI group compared to the healthy control group. These data indicated that HLA-B*44:03, C*07:01, DQB1*02:02 and DRB1*07:01 were related to OBI infection, whereas HLA-DRB1*08:03, DRB1*15:01 and DQB1*06:02 alleles were associated with HBV DNA clearance in a Shaanxi Han population.

Conclusions: The results of the present study suggest that host HLA gene is an important influencing factor for OBI pathogenesis.

Keywords: HLA; OBI; association analysis; gene polymorphism; heterozygote.