Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, CP 04510 CDMX, Mexico.
Department of Genetics, Instituto Nacional de Ciencias Médicas y de la Nutrición Salvador Zubirán, CDMX, Mexico.
J Immunol Res. 2020 Jan 29;2020:2965697. doi: 10.1155/2020/2965697. eCollection 2020.
Tuberculosis is still a global public health problem, with an estimated 10 million new cases and 1.6 million deaths in 2017. Of all humans infected with , only 10-15% will develop active tuberculosis disease during their lifetime, and data suggest that along with environmental factors, genetic factors influence susceptibility to develop active disease. Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the initiation and shaping of adaptive immune responses, and several TLRs have been shown to recognize mycobacterial components. In this work, we performed a case-control study to determine if common single nucleotide polymorphisms (SNPs) in genes encoding TLRs 1, 2, 4, 6, and 10 are associated with susceptibility to develop active tuberculosis in population from the state of Veracruz, Mexico. The study included 279 cases and 569 controls. The results show that the frequency of two SNPs in TLR4 was significantly higher in controls than in tuberculosis patients. The minor allele (G) of rs4986790 in (D299G) decreased the risk of active tuberculosis in the allelic (A vs. G, OR = 0.31, 95%CI = 0.09-0.81, = 0.01) and in the dominant genetic model (AA vs. GG+AG, OR = 0.26, 95%CI = 0.09-0.77, = 0.02). Similarly, the minor allele (T) of rs4986791 in (T399I) decreased the risk of active disease in the allelic model (C vs. T, OR = 0.29, 95%CI = 0.10-0.90, = 0.03). We did not find an association of SNPs in (N248S), (R753Q), (S249P), and (A153S and V298I) with tuberculosis disease. These results suggest that in this population, genetic variants of affect the susceptibility for suffering active tuberculosis disease.
结核病仍然是一个全球性的公共卫生问题，据估计，2017 年有 1000 万例新发病例和 160 万人死亡。在所有感染的人中，只有 10-15%会在一生中发展为活动性结核病，数据表明，除了环境因素外，遗传因素也会影响发病的易感性。Toll 样受体 (TLR) 是模式识别受体，在启动和塑造适应性免疫反应中起核心作用，已经有几种 TLR 被证明可以识别分枝杆菌成分。在这项工作中，我们进行了一项病例对照研究，以确定编码 TLRs 1、2、4、6 和 10 的基因中的常见单核苷酸多态性 (SNP) 是否与墨西哥韦拉克鲁斯州人群中发展为活动性结核病的易感性有关。该研究包括 279 例病例和 569 例对照。结果表明，TLR4 中两个 SNP 的频率在对照组中明显高于结核病患者。rs4986790 中的 minor 等位基因 (G) （D299G）降低了活动性结核病的风险（等位基因 A 对 G，OR = 0.31，95%CI = 0.09-0.81， = 0.01）和显性遗传模型（AA 对 GG+AG，OR = 0.26，95%CI = 0.09-0.77， = 0.02）。同样，rs4986791 中的 minor 等位基因 (T) （T399I）降低了活动性疾病的风险在等位基因模型中（C 对 T，OR = 0.29，95%CI = 0.10-0.90， = 0.03）。我们没有发现 SNPs 在 （N248S）、（R753Q）、（S249P）和 （A153S 和 V298I）与结核病之间存在关联。这些结果表明，在该人群中，TLR 的遗传变异影响了患活动性结核病的易感性。
