High levels of plasma interferon gamma and +874T/A gene polymorphism is associated with HIV-TB co-infection.

OBJECTIVE: Tuberculosis (TB) is one of the most frequent opportunistic infections in HIV patients leading to increased morbidity and death rate. This study was carried out to investigate the role of the cytokines IFN-γ and TNF-α level and their single nucleotide polymorphisms (SNPs) in HIV-TB co-infection.

METHODS: 247 HIV-TB (124 HIV-pulmonary TB, 123 HIV-extra pulmonary TB), 126 HIV positive individuals without tuberculosis and 129 healthy subjects (HS) were included to measure plasma levels of IFN-γ and TNF-α by sandwich ELISA and One way ANOVA statistical analysis was carried out among the groups. The SNPs of TNF-α-308 G/A, -238 G/A and IFN-γ+874 T/A were also investigated using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). The frequencies between the groups were compared by Pearson's chi square statistical analysis.

RESULTS: Plasma IFN-γ and TNF-α were significantly elevated in HIV-TB and TB (p<0.05) as compared to those in HS group. There was significant association between IFN-γ+874 'A' allele and AA genotype in HIV-TB groups compared to HS and HIV (p<0.05) and no such association was found for TNF-α-308 and -238. The plasma cytokine levels of TNF-α and IFN-γ reveals no significant association with levels of IFN-γ+874 T/A, TNF-α -308 G/Aand-238 G/A genotypes in any of the study groups.

CONCLUSION: In conclusion, the present study revealed elevated plasma IFN-γ and its +874 'A' allele are associated with HIV-TB co-infection indicating 1.6 times increased risk for TB susceptibility. Elevated TNF-α levels in TB and HIV-TB suggest its involvement in TB pathogenesis.