Single Nucleotide Polymorphisms in TLR4 Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz

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 M. tuberculosis, 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 TLR4 (D299G) decreased the risk of active tuberculosis in the allelic (A vs. G, OR = 0.31, 95%CI = 0.09‐0.81, p = 0.01) and in the dominant genetic model (AA vs. GG+AG, OR = 0.26, 95%CI = 0.09‐0.77, p = 0.02). Similarly, the minor allele (T) of rs4986791 in TLR4 (T399I) decreased the risk of active disease in the allelic model (C vs. T, OR = 0.29, 95%CI = 0.10‐0.90, p = 0.03). We did not find an association of SNPs in TLR1 (N248S), TLR2 (R753Q), TLR6 (S249P), and TLR10 (A153S and V298I) with tuberculosis disease. These results suggest that in this population, genetic variants of TLR4 affect the susceptibility for suffering active tuberculosis disease.