Association of single nucleotide polymorphisms of interferon-γ with pulmonary tuberculosis in population of Himachal Pradesh, India.

Interferon-gamma (IFN-γ) plays an integral role in the host immunity against tuberculosis (TB). The gene encoding IFN-γ is polymorphic and several studies have reported the association of its genetic polymorphisms with TB in different populations of the world. The present study investigated the association of rs2069705 (C/T), rs1861494 (C/T), rs1861493 (A/G) and rs2069718 (C/T) single nucleotide polymorphisms (SNPs) of IFN-γ with pulmonary TB in a population of Himachal Pradesh, India. For present study, 210 pulmonary TB patients and 205 healthy controls (HCs) were recruited. The selected SNPs of IFN-γ were genotyped by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and plasma IFN-γ levels were measured by ELISA. The 'T' allele of rs1861494 SNP was found to increase susceptibility to TB in the studied population (OR=2.18, 95%CI=1.57-3.03; p<0.001). After stratifying the subjects on basis of sex, males with 'T' allele of rs2069718 SNP were found to be at higher risk to TB (OR=1.55, 95%CI=1.07-2.25; p=0.02). We also found moderate linkage disequilibrium among the studied SNPs. The haplotypes C-T-A-T and T-T-G-T of rs2069705-rs1861494-rs1861493-rs2069718 were overrepresented in TB patients and found to increase susceptibility to TB (p=0.012). The plasma IFN-γ levels in TB patients were around seven times higher in comparison to HCs (p<0.0001). The HCs with genotype 'AA' of SNP rs1861493 were found with higher plasma IFN-γ levels than 'AG/GG' genotype (p=0.023). In conclusion, the results suggest t...