Toll-Like Receptor -1, -2, and -6 Polymorphisms and Pulmonary Tuberculosis Susceptibility: A Systematic Review and Meta-Analysis

Abstract

<div><p>Background</p><p>A large number of studies have investigated whether polymorphisms in the Toll-like receptor (TLR) genes are implicated in susceptibility to tuberculosis (TB) in different populations. However, the results are inconsistent and inconclusive.</p><p>Methods</p><p>A literature search was conducted using the PubMed, EMBASE, Medline (Ovid), ISI Web of Knowledge and Chinese National Knowledge Infrastructure (CNKI). A meta-analysis on the associations between the <i>TLR1</i> G1805T, <i>TLR2</i> T597C, T1350C, G2258A, and <i>TLR6</i> C745T polymorphisms and TB risk was carried out by comparison using different genetic models.</p><p>Results</p><p>In total, 16 studies from 14 articles were included in this review. In meta-analysis, significant associations were observed between the <i>TLR2</i> 2258AA (AA vs. AG+AG, OR 5.82, 95% CI 1.30–26.16, <i>P</i> = 0.02) and TLR6 745TT (TT vs. CT+CC, OR 0.61, 95% CI 0.39–0.97, <i>P = </i>0.04) polymorphisms and TB risk. In the subgroup analysis by ethnicity, Africans and American Hispanic subjects with the <i>TLR1</i> 1805T allele had an increased susceptibility, whereas Asian and European subjects with the <i>TLR2</i> 2258A allele had an increased susceptibility to TB.</p><p>Conclusions</p><p>The meta-analysis indicated that <i>TLR2</i> G2258A is associated with increased TB risk, especially in Asians and Europeans. <i>TLR1</i> G1805T is associated with increased TB in Africans and American Hispanics. <i>TLR6</i> C745T is associated with decreased TB risk. Our systematic review and meta-analysis reported an interesting preliminary conclusion, but this must be validated by future large-scale and functional studies in different populations.</p></div