Abstract
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.
Highlights
Tuberculosis (TB), an infectious disease usually caused by Mycobacterium tuberculosis (Mtb), is a global public health problem, with an estimated 10 million new cases of TB and 1.6 million deaths in 2017 [1]
We used a case-control population study design to evaluate whether single nucleotide polymorphisms (SNPs) in genes for various Toll-like receptors (TLRs) were associated with an increased risk to develop active TB disease in Mexican adults from the state of Veracruz
Our results suggest that the variant allele (G) in the polymorphism TLR4 D299G (A/G) and the variant allele (T) in polymorphism TLR4 T399I (C/T) on TLR4 gene confer a protective effect against active TB in this population
Summary
Tuberculosis (TB), an infectious disease usually caused by Mycobacterium tuberculosis (Mtb), is a global public health problem, with an estimated 10 million new cases of TB and 1.6 million deaths in 2017 [1]. Infection with Mtb can result in the development of active TB disease or in an immune response that can maintain the infection in a latent state (>85% of infected individuals). Latent TB can progress to active disease. Many factors affect the outcome of the initial infection and determine the progression from latent infection to active disease. In addition to factors such as age, gender, microbial infections, chronic diseases, and environmental aspects, there is strong evidence that genetic factors are important in determining the individual susceptibility to develop active TB [2]
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