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

Chi-Wei Liu,Lawrence Shih-Hsin Wu,Shih-Wei Lee,Hsiu-Jung Liu,Chou-Jui Lin,Hui-Chun Hu,Yu-Chi Chiu

doi:10.1038/s41598-020-67299-6

Chi-Wei Liu, Lawrence Shih-Hsin Wu + Show 5 more

Open Access

https://doi.org/10.1038/s41598-020-67299-6

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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.

Highlights

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that mostly affects the lungs
In our study of the Taiwanese population, we found that the TC genotype of NLRP3 rs34298354 was associated with decreased risk of TB
We found that the C-T haplotype of toll‐like receptor 2 (TLR2) rs3804099-rs3804100 was associated with increased susceptibility to TB

Summary

Introduction

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that mostly affects the lungs. Few reports have evaluated the association of AIM2 and IFI16 gene polymorphisms with TB risk. TLRs are pattern recognition receptors expressed in antigen‐presenting cells and are important in host immunity to infectious pathogens[18,19]. They are involved in the recognition of Mtb and are linked to inflammasome activation[20]. Whether other TLR2 polymorphisms are associated with genetic susceptibility to TB in the Han Taiwanese population is still unknown. In light of the above information, we proposed that variants in inflammasome genes and TLR2 could influence the host response to Mtb infection and the development of TB. Our results indicate that genetic variants of inflammasome and TLR2 genes are associated with TB risk in the Han Taiwanese population

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