Association of polymorphisms of innate immunity-related genes and tuberculosis susceptibility in Mongolian population

Hum Immunol. 2021 Apr;82(4):232-239. doi: 10.1016/j.humimm.2021.02.008. Epub 2021 Mar 7.

Abstract

Backgrounds: Genetic polymorphism of the toll-like receptor 2, 4 (TLR2, TLR4) and natural resistance-associated macrophage protein 1 (NRAMP1) genes may affect host immune response to Mycobacterium tuberculosis (Mtb) and lead to the variation of susceptibility to tuberculosis (TB) in humans. However, the association of single nucleotide polymorphisms (SNP) in these genes and the susceptibility to TB in Mongolian population has not been investigated.

Methods: We conducted a genetic association study including 197 Mongolian TB patients and 217 Mongolian healthy controls in Inner Mongolia, China. DNA of blood samples was extracted and genotyped for 5 SNPs in TLR4, 4 SNPs in TLR2 and 5 SNPs in NRAMP1 by next-generation sequencing. A logistic regression was performed and odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the risk at TB by each SNP.

Results: The most significant locus associated with the susceptibility to TB was TLR4 rs11536889. The frequency for allele C of TLR4 rs11536889 was 16.0% in TB patients and 23.5% in healthy controls, respectively. Rs11536889 C/C genotype of TLR4 was significantly associated with the low susceptibility against TB compared to G/G genotype in the dominant model (OR 0.62, 95% CI 0.41-0.94).

Conclusions: The TLR4 rs11536889 polymorphisms might be an indicative of the low susceptibility to TB in Mongolian population, which provides valuable information for the generation of effective strategy or measurement against TB in Mongolian population.

Keywords: Mongolian; NRAMP1; SNP; TLR2; TLR4; Tuberculosis.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cation Transport Proteins / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype*
  • Humans
  • Immunity, Innate / genetics
  • Male
  • Middle Aged
  • Mongolia / epidemiology
  • Mycobacterium tuberculosis / physiology*
  • Polymorphism, Single Nucleotide
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 4 / genetics*
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / genetics*
  • Tuberculosis, Pulmonary / immunology

Substances

  • Cation Transport Proteins
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • natural resistance-associated macrophage protein 1