Associations of the Polymorphisms of the NHEJ Pathway Genes With HIV-1 Infection and Aids Progression Among Men Who Have Sex With Men in Northern China

Abstract Background: Men who have sex with men (MSM) are at high risk of HIV infection. Non-homologous end joining (NHEJ) pathway is the main way of double-stranded DNA break (DSB) repair in the higher eukaryotes, and can repair the DSB timely at any time in cell cycle. The objective of this study was to investigate the association of SNPs of the NHEJ pathway genes with susceptibility to HIV-1 infection and AIDS progression among MSM residing in northern China.Results: In the present study, a total of 481 HIV-1 seropositive men and 493 HIV-1 seronegative men were included. And genotyping of 22 SNPs in NHEJ pathway genes was performed using the SNPscanTM Kit. Our results disclosed significant associations of XRCC6 rs132770 and XRCC4 rs1056503 genotypes with susceptibility to HIV-1 infection. The generalized multifactor dimensionality reduction (GMDR) analysis found a significant SNP-SNP interaction between the XRCC6 and XRCC4 variants in the risk of HIV-1 infection. In stratified analysis, the positive effects of XRCC5 rs16855458 and LIG4 rs1805388 on the CD4+ T cell count and clinical phase of disease were validated.Conclusions: Our results confirmed that the NHEJ gene polymorphisms played an important role in HIV-1 infection and AIDS progression in the northern Chinese MSM population.