Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, China.
Faculty of Health Sciences, OsloMet - Oslo Metropolitan University, Oslo 1346, Norway.
Hum Immunol. 2021 Apr;82(4):232-239. doi: 10.1016/j.humimm.2021.02.008. Epub 2021 Mar 7.
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.
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.
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).
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.
Toll 样受体 2、4（TLR2、TLR4）和天然抗性相关巨噬细胞蛋白 1（NRAMP1）基因的遗传多态性可能影响宿主对结核分枝杆菌（Mtb）的免疫反应，并导致人类对结核病（TB）易感性的变化。然而，这些基因中的单核苷酸多态性（SNP）与蒙古人群中 TB 的易感性之间的关联尚未被研究过。
我们在中国内蒙古进行了一项遗传关联研究，包括 197 名蒙古 TB 患者和 217 名蒙古健康对照。从血液样本中提取 DNA，并通过下一代测序对 TLR4 中的 5 个 SNP、TLR2 中的 4 个 SNP 和 NRAMP1 中的 5 个 SNP 进行基因分型。采用逻辑回归分析，计算每个 SNP 的 TB 风险的比值比（OR）和 95%置信区间（CI）。
与 TB 易感性最显著相关的位点是 TLR4 rs11536889。TLR4 rs11536889 的等位基因 C 在 TB 患者中的频率为 16.0%，在健康对照中的频率为 23.5%。与 G/G 基因型相比，TLR4 rs11536889 的 C/C 基因型在显性模型中与对 TB 的低易感性显著相关（OR 0.62，95%CI 0.41-0.94）。
TLR4 rs11536889 多态性可能是蒙古人群中对 TB 低易感性的一个指标，这为在蒙古人群中制定针对 TB 的有效策略或措施提供了有价值的信息。
