Polymorphisms in the ASAP1 and SP110 Genes and Its Association with the Susceptibility to Pulmonary Tuberculosis in a Mongolian Population.

Tuberculosis (TB) remains one of the deadliest infectious diseases in the world. Previous genome-wide association studies suggested that single-nucleotide polymorphisms (SNPs) in some genes could indicate the susceptibility to TB in some populations. Herein, we studied the association of SNPs in the immunity-related genes, i.e., ASAP1 and SP110 genes with the susceptibility to TB in a Mongolian population in China. A case-control study was performed with 197 TB patients and 217 healthy controls. Six SNPs in ASAP1 and six SNPs in SP110 were selected for genotyping test by second-generation sequencing technique. A SNP in SP110 gene (rs722555) was identified to be associated with susceptibility to TB in the Mongolian population (p < 0.05). The T allele of rs722555 in SP110 gene was associated with a 36% increase of risk at TB (OR 1.36, 95% CI 1.03-1.81), and the CT+TT genotype of rs722555 was associated with a 74% increase of risk at TB (OR 1.74, 95% CI 1.16-2.60) in the dominant genetic model. None of SNPs in ASAP1 gene tested in this study were significantly associated with TB susceptibility, while some individuals with SNPs (rs10956514, rs4733781, rs2033059, rs12680942, rs1017281, rs1469288, and rs17285138) in the ASAP1 gene tended to have a reduced risk at TB. In conclusion, this study suggested that the rs722555 SNP in SP110 gene might be a risk factor for TB in a Mongolian population.

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

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.