Abstract
Genetic polymorphisms for tuberculosis (TB) susceptibility have been researched by some studies, but few have studied multiple innate immunity genes associated with TB. Evidence suggests that the toll-like receptor 2, 4 (TLR2, TLR4) and toll interacting protein (TOLLIP) may be associated with TB susceptibility. In this self-validated study, we explored the association between common single nucleotide polymorphisms (SNPs) of TLR2, TLR4 and TOLLIP in the Chinese Han and Tibetan populations. A SNPscan™ method was used to genotype SNPs in the three genes. Multiple logistic regression adjusted by sex and age was used to detect the association between SNPs and TB. In TLR2, rs1898830 was associated with decreased risk against TB in the Chinese Han population, which was validated in the Tibetan population. In TLR4, rs11536889 was a protective factor for TB in the Tibetan population, but not in the Han population. Additionally, in the Tibetan population, we also found that the frequency of genotypes of TOLLIP rs11536889 differs significantly between TB patients and controls. We found rs1898830 in TLR2 was associated with TB susceptibility in both Chinese Han and Tibetan populations while rs11536889 in TLR4 and rs3750920 in TOLLIP were protective factors against TB in the Tibetan population.
Highlights
Tuberculosis (TB) remains a serious global health concern
A total of 636 TB cases and 608 TB-negative controls were recruited from the Chinese Han population for genetic analysis
In the initial Chinese Han population, the frequency of TLR2 rs1898830 G allele was lower in TB patients than in controls (P = 0.035, odds ratio (OR) = 0.84, 95% confidence interval (CI): 0.72–0.99), indicating it was a protective factor against TB
Summary
Tuberculosis (TB) remains a serious global health concern. In 2017, World Health Organization (WHO) estimated that approximately 10.4 million new TB cases were diagnosed and 1.7 million died from it, majorly in developing countries [1]. Almost one-third of the population is infected with Mycobacterium tuberculosis TB), only 10% of them develop active TB, indicating that there are discrepancies among individuals in the susceptibility to TB development. In addition to environmental factors, host genetic factors play an important role in TB vulnerability [2]. TB infections in both humans and mice have reported several potential TB causal genes, including genes related to toll-like receptor (TLR) signaling [3]
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