The association of inflammasome and TLR2 gene polymorphisms with susceptibility to tuberculosis in the Han Taiwanese population

Abstract

Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global public health concern. Although inflammasome and the toll-like receptor 2 (TLR2) genes play an important role in host defense against Mtb, the associations of polymorphisms in these genes with TB risk are incompletely understood. A total of 230 TB patients and 213 individuals without TB were enrolled in this study. A significant difference in the frequencies of different AIM2 rs2276405 genotypes between the non-TB and TB groups was detected. When the patients were stratified by gender or age, significant differences in genotype frequencies at NLRP3 rs34298354 in men and in non-aged (≤65-year-old) subjects and at IFI16 rs1772408 in women were found. OR analysis showed that the TC rs34298354 genotype in NLRP3 was associated with reduced risk of TB. In women, the AG rs1772408 genotype in IFI16 was associated with decreased TB risk. Haplotype analysis showed that, in comparison with the most common haplotype (T-T) of rs3804099-rs3804100 in the TLR2 gene, the C-T haplotype was associated with an increased risk for TB. Our study indicates that rs34298354 in NLRP3 and rs1772408 in IFI16 protect individuals from TB, and that the less common TLR2 haplotype is associated with increased TB susceptibility.

Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

“…AIM2 binds to HIV dsDNA and may trigger acute inflammation and pyroptosis ( Ekabe et al., 2021 ). Regarding the AIM2 rs2276405 polymorphism, to our knowledge, only one study showed a significant difference in the genotype frequencies of this Single Nucleotide Polymorphism (SNP) between individuals with and without TB in a Taiwanese population ( Liu et al., 2020 ). In our study, no association between AIM2 polymorphisms and the occurrence of TB or its clinical presentations or inflammasome-related cytokines was observed.…”

Single-Nucleotide Variants in the AIM2 – Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis

“…Studies regarding human genetic variants of AIM2 are rare in infectious diseases ( 41 , 42 , 45 ). Recently, we investigated another SNV of AIM2 (rs35130877) in 288 patients with PTB and 288 HCs.…”

Resistance and Susceptibility Immune Factors at Play during Mycobacterium tuberculosis Infection of Macrophages

“…A case-control study of a Chinese Han cohort identified SNPs in PRRs, TLR8, and TLR9, which were found to be associated with the development of TB [ 178 ]. In another study with a Han Taiwanese population [ 179 ], the C-T haplotype in the TLR2 gene, in comparison with the most common T-T haplotype, was associated with an increased risk for TB. There is evidence to justify further evaluation of TLR2 polymorphisms and their effect on TLR2-dependent signaling as these findings can provide insight into the development of TB therapeutics [ 195 ].…”

“…Lastly, although not a receptor involved in the phagocytosis or uptake of M.tb , multiple recent studies have examined polymorphisms in the vitamin D receptor (VDR) in different populations for their association with increased susceptibility to TB infection [ 183 , 184 , 185 , 197 ]. Other important immune factors in which SNPs have been recently studied include NLRP3 [ 186 ], AIM2 [ 179 , 187 ], and C-type lectins [ 188 , 189 ].…”