Association of HLA-G 3’UTR Polymorphisms with hepatitis B virus infection in Tunisian population

Abstract

Background Hepatitis B virus (HBV) infection is a major public health burden. The mechanisms of immune evasion during chronic HBV (CHB) infection are poorly understood. Human leukocyte antigen (HLA)-G, an immune checkpoint molecule, plays a crucial role in the tolerance mechanisms of various infectious diseases. The 3’untranslated region (3’UTR), including the HLA-G + 3142C > G polymorphism (rs1063320) and the 14-pb Ins/Del (rs66554220) has been strongly suggested to influence HLA-G expression. Objective This study conducted a case-control analysis to evaluate the potential correlation between the HLA-G + 3142 C > G polymorphism and HBV infection outcome in a Tunisian cohort. Methods The HLA-G + 3142C > G polymorphism was analysed by PCR-RFLP in 242 patients with chronic HBV infection, 241 healthy controls, and 100 spontaneously resolved subjects. Results Patients with chronic HBV infection showed a higher frequency of the + 3142 G allele compared to healthy controls and spontaneously resolved subjects (p = 0.001 and p = 0.002, respectively). An association between the + 3142 G allele and high HBV DNA levels was observed when HBV patients were stratified based on their HBV DNA levels (p = 0.016). Furthermore, the dominant model (GG + GC vs CC) was associated with liver function parameters, including AST, ALT, and high HBV DNA levels (p = 0.04, p < 0.001 and p = 0.002, respectively). However, there was no significant association found between this polymorphism and the fibrosis stage (p = 0.32). The haplotype analysis, using a subset of previously published data on the HLA-G 14pb Ins/Del polymorphism, revealed an association between the Ins/G haplotype and chronic HBV infection (H1: InsG, p < 0.001). Conclusion Our findings suggest that the + 3142 G allele is a risk factor for the persistence and progression of HBV infection, while the + 3142 C allele serves as a protective allele associated with the spontaneous resolution of the infection. Additionally, the HLA-G 3’UTR haplotype Ins/G is associated with chronic HBV infection in the Tunisian population.