Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts

Abstract

BackgroundTo investigate whether the toll-like receptor 2 polymorphisms could influence susceptibility to pulmonary TB, its phenotypes, and blood lymphocyte subsets.MethodsA total of 368 subjects, including 184 patients with pulmonary TB and 184 healthy controls, were examined for TLR2 polymorphisms over locus -100 (microsatellite guanine-thymine repeats), -16934 (T>A), -15607 (A>G), -196 to -174 (insertion>deletion), and 1350 (T>C). Eighty-six TB patients were examined to determine the peripheral blood lymphocyte subpopulations.ResultsWe newly identified an association between the haplotype [A-G-(insertion)-T] and susceptibility to pulmonary TB (p = 0.006, false discovery rate q = 0.072). TB patients with systemic symptoms had a lower -196 to -174 deletion/deletion genotype frequency than those without systemic symptoms (5.7% vs. 17.7%; p = 0.01). TB patients with the deletion/deletion genotype had higher blood NK cell counts than those carrying the insertion allele (526 vs. 243.5 cells/μl, p = 0.009). TB patients with pleuritis had a higher 1350 CC genotype frequency than those without pleuritis (12.5% vs. 2.1%; p = 0.004). TB patients with the 1350 CC genotype had higher blood NK cell counts than those carrying the T allele (641 vs. 250 cells/μl, p = 0.004). TB patients carrying homozygous short alleles for GT repeats had higher blood NK cell counts than those carrying one or no short allele (641 vs. 250 cells/μl, p = 0.004).ConclusionsTLR2 genetic polymorphisms influence susceptibility to pulmonary TB. TLR2 variants play a role in the development of TB phenotypes, probably by controlling the expansion of NK cells.

Genetic diversity of TLR2, TLR4, and VDR loci and pulmonary tuberculosis in Moroccan patients

“…Of note, the TLR2 -16934 and +1349 single SNPs did not have statistically significant individual effects. Altogether, these observations are consistent with a recent study involving Taiwanese PTB patients, reporting an association between a specific TLR2 haplotype including the TLR2 -16934 SNP and PTB susceptibility rather than this SNP alone [34]. This suggests that this variant may act through an additive effect in the presence of other genetic variations.…”

Mycobacterium tuberculosis Lipoproteins Directly Regulate Human Memory CD4 + T Cell Activation via Toll-Like Receptors 1 and 2

“…Polymorphisms in TLR2 have been associated with an increased risk of TB in different populations (13,38,52), as well as with severe, disseminated forms of TB (11,35,51). Although these genetic association studies cannot provide a direct causal relationship between TLR2/1 polymorphisms and risk of TB, they do suggest that TLR2 signaling may have a role in development of protective immune responses to M. tuberculosis.…”

The toll‐like receptor 2 (TLR2) ‐196 to ‐174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C

“…Genetic studies on the TLR2 gene have identified a number of polymorphisms which have been shown to affect host defense and disease progression. 8,9 A 22-bp nucleotide deletion at position -196 to -174 of the untranslated 5 0 -region is associated with reduced transcriptional activity compared to the wild type allele in luciferase reporter assays. 10 This polymorphism has already been shown to be associated with an increased risk of noncardiac gastric cancer and susceptibility to cervical cancer.…”