Single nucleotide polymorphism rs2234711 of interferon gamma receptor 1 is associated with pulmonary tuberculosis in the population of North India.

Interferon-gamma (IFN-γ) is a pro-inflammatory cytokine playing essential role in immunity against tuberculosis (TB). IFN-γ performs function by binding to its receptor complex, consisting of two polypeptide chains viz. IFN-γ receptor 1 (IFN-γR1) and IFN-γ receptor 2 (IFN-γR2). Structural and functional deficiencies in IFN-γR1 can make individual vulnerable to even weak mycobacterial infections. Studies from different populations of the world have reported the association of single nucleotide polymorphisms (SNPs) present in IFNGR1 gene with TB, however, there are no such studies from India. Thus, the present study was designed to analyse the association of rs2234711 (C/T), rs7749390 (C/T) and rs1327475 (C/T) SNPs of IFNGR1 with TB in the population of North India. For the present study, 263 TB patients (at zero day of anti-tuberculosis therapy) and 256 healthy controls (HCs) were recruited. The genotyping of selected SNPs was done by high-resolution melting (HRM) curve analysis. The mRNA and surface expression data of IFNGR1 was extracted from our previous study and was grouped according to the genotypes of studied SNPs. The genotype 'TT' and 'T' allele of SNP rs2234711 (C/T) were found to be associated with TB in studied population ['T' vs 'C': OR (CI) = 1.79 (1.39-2.29); p-value < 0.0001]. The haplotypes 'C-C-C' of rs2234711-rs7749390-rs1327475 confers protection, while haplotype 'T-C-C' is a risk factor for TB in studied population. It was also found that 'TT' genotype of rs2234711 in HCs is associated with lower surface expression of IFNGR1 (p-value = 0.0078). In conclusion, 'TT' genotype is associated with lower surface expression of IFNGR1 and is increasing the susceptibility to TB in North Indian population.

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 the association of rs1861494 (C/T) and rs2069718 (C/T) SNPs of IFN-γ with TB and genotype 'AA' of rs1861493 is associated with higher plasma IFN-γ levels in the population of Himachal Pradesh, India.