Association of NOS2A Gene Polymorphisms with Susceptibility to Tuberculosis in Manipuri Population of Northeast India.

Abstract

Single nucleotide polymorphisms (SNPs) have been reported to influence the activity of specific genes involved with the innate immune response to Mycobacterium; hence, they are crucial in tuberculosis (TB) susceptibility studies. The study aimed to investigate the polymorphism in the NOS2A (Nitric oxide synthase 2A) gene and its association with susceptibility to TB in the Manipuri population of northeast India. This case-control study includes 495 subjects- 220 TB patients and 275 control individuals. TaqMan allelic discrimination assay was used to study the gene polymorphism, and Griess's test was employed to determine the serum nitric oxide (NO) levels. Serum NO levels were analysed to correlate with the functional changes associated with the polymorphisms. Two SNPs of the gene, NOS2A (rs8078340 and rs2274894), were studied. For the SNP-rs8078340, a significant difference in the genotypic and allelic frequencies was observed between the cases and control groups (p = 0.001; AA genotype OR = 30.288, 95% CI: 1.703-538.44 and A allele OR = 2.937, 95% CI: 1.762-4.896). However, for the SNP-rs2274894, only the T allele (with OR = 1.464; 95% CI: 1.080-1.983, p = 0.014) was associated with susceptibility to TB. Serum levels of NO were significantly different between the cases and control groups (p < 0.05). Significant associations of both homozygous AA genotype and allele A of the NOS2A (rs8078340) and minor allele T of NOS2A (rs2274894) were observed with susceptibility to TB. Patients with the AA genotype of NOS2A show a higher NO level, suggesting its role in greater expression of the NOS2A gene.