Single Nucleotide Polymorphisms inTLR4Affect Susceptibility to Tuberculosis in Mexican Population from the State of Veracruz

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.

Neutrophil autophagy during human active tuberculosis is modulated by SLAMF1

“…influence the pathology and the immune responses against Mtb [37][38][39][40][41][42]. Indeed, single nucleotide polymorphisms may influence the differential SLAMF1 expression on neutrophils from TB patients and HD.…”

Immune and inflammation‐related gene polymorphisms and susceptibility to tuberculosis in Southern Xinjiang population: A case‐control analysis

“…To date, the results on the relationship between TLR gene polymorphisms and tuberculosis are not consistent, especially when they are performed in different populations. For example, Ortega et al found that the G allele of rs4986790 in TLR4 was associated with a reduced risk of tuberculosis in the Mexican population (Ortega et al, 2020).…”

“…Similarly, there is no significant correlation between IFNGR1 rs1327474 and the risk/protection of pulmonary tuberculosis (Naderi et al, 2015). The research results of the relationship between the rs4986790 gene polymorphism in TLR4 and tuberculosis are inconsistent in different populations (Ortega et al, 2020;Thada et al, 2013;Zhou & Zhang, 2020;L. Zhao et al, 2015).…”

Toll-Like Receptors and Mannose Binding Lectin Gene Polymorphisms Associated with Cryptosporidial Diarrhea in Children in Southern India

“…28 In a more recent study by Ortega et al, the minor allele G was also associated with deceased risk of active tuberculosis (OR 5 0.31). 29 A meta-analysis of genetic susceptibility studies showed an increased odds of parasitic infections associated with this SNP, but none of the studies included in the analysis involved Cryptosporidium or any other gastrointestinal parasite. 30 The TIRAP gene encodes an adaptor protein that is essential for downstream signaling of TLR2 and TLR4.…”