Protective effects of HLA-DPA1/DPB1 variants against Hepatitis B virus infection in an Indonesian population

• HLA DPA1/DPB1 including rs3077, rs9277535, and rs3135021 influenced the clinical outcomes of HBV infected Indonesian population.
• The CT and TT genotype of HLA-DPA1 rs3077 variants were associated with a protective effect increasing the spontaneously resolved of HBV infection.
• The GA and AA genotype of HLA-DPB1 rs9277535, as same as the A allele, were associated with a reduced risk of persistent HBV infection.
• Combinations of haplotype markers (CA for rs3077–rs9277535 and GA for rs3135021–rs9277535) were associated with HBV susceptibility

ABSTRACTHuman leukocyte antigen (HLA) DPA1/DPB1 variants have been reported to influence Hepatitis B virus (HBV) infection. HLA-DPA1/DPB1 plays a pivotal role in antigen presentation to CD4+ helper T cells and influences the outcome of HBV infection. To investigate the influence of HLA-DP variants on the outcome of HBV infection in an Indonesian population where it has the third-highest prevalence of HBV infection worldwide, we performed a case–control study of 686 participants, including patients with HBV-related advanced or nonadvanced liver disease, patients with spontaneously resolved HBV, and healthy controls. Single-nucleotide polymorphisms in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs228388) were genotyped using real-time TaqMan® genotyping assays. Because rs2281388 deviated from Hardy–Weinberg equilibrium, it was excluded from subsequent analyses. The results of logistic regression analyses showed that the HLA-DPB1 rs9277535 variants were associated with a reduced risk of persistent HBV infection (odds ratio [OR] 0.70, 95% confidence interval [95% CI] 0.52–0.96, P = 0.026, additive genetic model; OR 0.60, 95% CI 0.38–0.96, P = 0.033, dominant genetic model). The HLA-DPA1 rs3077 variant was associated with a protective effect increasing the spontaneously resolved HBV infection (OR 0.64, 95% CI 0.41–0.98, P = 0.039, dominant genetic model). By contrast, the HLA-DPB1 rs3135021 variant was not associated with the outcome of HBV infection, including susceptibility, spontaneously resolved, or disease progression. Combinations of haplotype markers were also associated with HBV susceptibility (CA for rs3077–rs9277535, OR 0.57, 95% CI 0.36–0.92, P = 0.021; GA for rs3135021–rs9277535, OR 0.56, 95% CI 0.36–0.86, P = 0.0087). In conclusion, these findings confirm that HLA-DPA1/DPB1 variants were associated with the outcomes of HBV infection in an Indonesian population.