Amino acids at positions 30β1 and 57β1 of HLA-DR confer susceptibility to or protection from chronic hepatitis B virus infection

This study is to investigate whether structures and electrostatic potentials of human leukocyte antigen (HLA)-DRB1 molecules are relative to the outcomes of hepatitis B virus (HBV) infection. Totally 230 subjects were categorized into the recovered HBV infection group (RH, n = 86) and the chronic HBV infection group (CH, n = 144). Genotypes and amino acid sequences of HLA-DRB1 were obtained. Structure templates suitable for modeling were checked in Protein Data Bank. The atomic coordinates of HLA-DR molecules were determined by MODELLER computer algorithm. The analyses for the polymorphic residues of HLA-DRB1 proteins were performed using the stepwise logistic regressions. CH and RH-associated polymorphic residues 57, 30, and 28 had more significant associations with the outcomes of HBV infection compared with other residues according to “Allele” model. CH and RH-associated polymorphic residues 30 and 57 had more significant associations with the outcomes of HBV infection compared with other residues according to “Genotype” model. Polymorphic residues 14, 16, 25, 28, 30, 37, 38, 57 and 85 were significant residues according to “Allele” model. HLA alleles carried significant residues. Special residues influenced the electrostatic properties of HLA-DRB1 pockets. The residues Lys14, Tyr16, Gln25, Glu28, His/Leu30, Leu37, Leu38, Val57 and Ala85, especially His/Leu30 and Val57, in chronic HBV population were significantly enriched. This suggests that the residues 14, 16, 25, 28, 30, 37, 38, 57 and 85, especially 30 and 57, in the HLA-DR β chain critically influence the structural and electrostatic properties of the peptide-binding groove.