Toll-like receptor and matrix metalloproteinase single-nucleotide polymorphisms, haplotypes, and polygenic risk score differentiated between tuberculosis disease and infection

Meng-Rui Lee; Yen-Lin Chen; Chang-Wei Wu; Lun-Che Chen; Lih-Yu Chang; Jung-Yueh Chen; Yu-Tsung Huang; Jann-Yuan Wang; Jin-Yuan Shih; Chong-Jen Yu

doi:10.1016/j.ijid.2022.10.020

Toll-like receptor and matrix metalloproteinase single-nucleotide polymorphisms, haplotypes, and polygenic risk score differentiated between tuberculosis disease and infection

Int J Infect Dis. 2022 Dec:125:61-66. doi: 10.1016/j.ijid.2022.10.020. Epub 2022 Oct 19.

Authors

Affiliations

¹ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
² Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
³ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch Biomedical Park Hospital, Hsin-Chu, Taiwan.
⁴ Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; College of Medicine, I-Shou University, Kaohsiung, Taiwan.
⁵ Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁶ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: jywang@ntu.edu.tw.
⁷ Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch Biomedical Park Hospital, Hsin-Chu, Taiwan.

PMID: 36272698
DOI: 10.1016/j.ijid.2022.10.020

Abstract

Objectives: The association of toll-like receptors (TLRs) and matrix metalloproteinases (MMPs) single-nucleotide polymorphisms (SNPs) among latent tuberculosis (TB) infection and active TB remained less studied.

Methods: We recruited participants with TB disease (active TB) (n = 400) and TB infection (latent TB infection) (n = 203) in this study. We genotyped SNPs in TLR1, TLR2, TLR4, MMP1, MMP8, MMP9, MMP12, and tissue inhibitor of MMP2. Single-variant analysis and haplotype analysis were performed, and a polygenic risk score (PRS) was created.

Results: We found that SNPs in TLR1 (rs5743580, rs5743551), TLR2 (rs3804100), and MMP8 (rs2508383) were associated with different TB disease status risks. TLR1 rs5743580 was associated with a higher risk of TB disease status in genotypic, recessive, and additive models. TLR2 rs3804100 polymorphisms demonstrated significant association with TB disease status in genotypic, dominant, and additive models. In the haplotype analysis, the TLR1 haplotype was associated with a higher risk of TB disease, and the MMP12 haplotype was associated with a lower risk of TB disease. A PRS using 3 SNPs was associated with a higher risk of TB disease.

Conclusion: This study revealed that SNP variants in TLR1, TLR2, and MMP8 differed among TB infection and disease. Haplotypes and PRS could potentially help predict TB disease status.

Keywords: Latent tuberculosis infection; Matrix metalloproteinase; Single-nucleotide polymorphism; Toll-like receptor; Tuberculosis.

MeSH terms

Case-Control Studies
Genetic Predisposition to Disease
Haplotypes
Humans
Latent Tuberculosis*
Matrix Metalloproteinase 12 / genetics
Matrix Metalloproteinase 8 / genetics
Matrix Metalloproteinases* / genetics
Polymorphism, Single Nucleotide
Risk Factors
Toll-Like Receptor 1 / genetics
Toll-Like Receptor 2 / genetics
Toll-Like Receptors* / genetics
Tuberculosis* / genetics

Substances

Matrix Metalloproteinase 12
Matrix Metalloproteinase 8
Toll-Like Receptor 1
Toll-Like Receptor 2
Toll-Like Receptors
Matrix Metalloproteinases