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

Interferon-gamma (IFN-gamma) plays an integral role in the host immunity against tuberculosis (TB). The gene encoding IFN-gamma 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-gamma 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-gamma were genotyped by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and plasma IFN-gamma 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-rs1861494rs1861493-rs2069718 were overrepresented in TB patients and found to increase susceptibility to TB (p = 0.012). The plasma IFN-gamma 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-gamma levels than 'AG/GG' genotype (p = 0.023). In conclusion, the results suggest the association of rs1861494 (C/T) and rs2069718 (C/T) SNPs of IFN-gamma with TB and genotype 'AA' of rs1861493 is associated with higher plasma IFN-gamma levels in the population of Himachal Pradesh, India.