HLA-DP and IL28B Polymorphisms: Influence of Host Genome on Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B

Abstract

The roles of single-nucleotide polymorphisms (SNPs) at HLA-DP and IL28B loci on hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) infection are unknown. We compared the HLA-DP (rs3077, rs9277378, rs3128917) and IL28B (rs12979860, rs8099917) polymorphisms of 203 CHB patients achieving spontaneous HBsAg seroclearance with 203 age- and sex-matched CHB patients without HBsAg seroclearance (controls). The distribution of all 5 polymorphisms was in Hardy-Weinberg equilibrium. HLA-DP rs3077 was associated with HBsAg seroclearance in terms of allelic frequency (minor allele A vs major allele G, P = .035; odds ratio [OR], 0.699; 95% confidence interval [CI], .501-.976) and genotypic frequency (AA vs GG/GA, P = .014; OR, 0.295; 95% CI, .106-.822). Haplotype analysis of HLA-DP polymorphisms showed haplotype block GAT (rs3077/rs9277378/rs3128917) to be associated with HBsAg seroclearance (OR, 2.17; 95% CI, 1.06-4.45, P = .034). Influence of HLA-DP polymorphisms on HBsAg seroclearance was more pronounced in younger patients, with the OR for rs3077 minor allele A and haplotype block GAT being 0.560 and 2.68, respectively, among patients aged <50 years (P = .027 and P = .047, respectively). IL28B haplotype block CG (rs12979860/rs8099917) was associated with HBsAg seroclearance (OR, 10.5, P = .026). None of the 5 polymorphisms influenced anti-HBs positivity among patients achieving HBsAg seroclearance, or serum HBV DNA and HBsAg titers among controls (P > .05). Specific SNPs in HLA-DP and IL28B locus, through individual and haplotype analysis, were associated with a higher chance of HBsAg seroclearance in CHB infection. The associations were more prominent in patients with HBsAg seroclearance at a younger age.