Immunodeficiency: primary or acquired
Host genetic factors may be one of the possible reasons for variable HIV-1 disease progression. The aimwas to determine the association of functional IFNγ gene and TNF-a SNPs and its associated parameters related to apoptosis that may influence the rate of HIV-1 disease progression. We planned to evaluate the association of certain SNPs in IFNγ gene and promotor region of TNFa gene with the susceptibility to or rate of progression of HIV disease.Therapy naive, 100 HIV slow progressors, 100 fast progressors, 50 HIV exposed seronegative individuals and 260 healthy controls from same ethnic origin were recruited. Genotyping of IFNγ (+874 T/A) and TNF-a variants (2863C/A, -308G/A and -238G/A) was done using PCR-RFLP. Genotype and allele frequency of IFN-γ+874 variants were observed to be 0.61% for ‘A’ allele and 0.39% for T-allele. Frequency of AA genotype (associated with low production of IFN-γ) was found to be significantly higher in fast progressors in comparison to slow progressors (p=0.017, OR= 2.76). While that of TNF-a -238G/A and -863C/A was not significantly different in HIV-1-infected patients when compared to controls, while that of TNF-a -308G/A variant (high TNF-a producer) was significantly higher in FPs compared to SPs (p,0.01, OR = 3.43). Haplotype analyses also showed that carriers of high TNF-a producing haplotype CAG was significantly more common among FPs compared to SPs (p,0.01, OR = 3). The lymphocyte mitochondrial membrane potential of FPs having CAG haplotype was significantly low as compared to wild type (CGG) haplotype (417622 vs 571628, p,0.01).