Investigation of certain genetic and immunological factors that could determine the outcome of hepatitis B infection in Indian individuals

Abstract

This study has established the association of certain host genetic determinants that can influence the outcome of HBV infection in the South Indian population. Considering the magnitude of HBV related disease and the unique population structure, there is a paucity of research in this area. This study has shown that the functional VDR polymorphism (FokI ffmutant genotype) was strongly associated with viral persistence. The VDR-ApaI aa-mutant genotype was highly linked to HBV DNA positivity in chronic HBV infection. TNF-and#945; -863 and - 1031 genotypes were significantly associated with HBV outcome. Individuals with TNF-and#945; -863 AA- mutant genotype had a substantial fourfold independent risk of progression to chronicity. TNF-and#945; -863 CA-genotype was significantly associated with HBV DNA negativity in chronic HBV infection. The mbl2 codon 52 mutant TC-genotype showed an unequivocal independent association with spontaneous recovery. This is the first study to identify heterozygote advantage of the mbl2 gene against HBV infection. The HLA-A*68, B*08, DRB1*03 and DRB1*13 alleles were significantly associated with spontaneous recovery whereas, HLA-B*44, B*57 and DRB1*07 alleles were significantly associated with chronic HBV infection. Individuals with HLA-B*44 allele had a six fold risk of progression to chronicity. The HLA-DRB1*07 allele which is predominantly seen in the South Indian population showed fourfold independent risk of progression to chronicity. The global HBV resistant allele (HLA-DRB1*13) conferred a substantial independent protection from chronicity. Hence, it is crucial to consider the burden and the outcome of HBV disease in the context of population specific genetic information rather than considering it in isolation. This study has provided a valuable host genetic evidence for the existing mysterious dichotomy in the outcome of HBV infection. newline