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Abstract
BackgroundPublications regarding the associations of toll-like receptor 2 (TLR2) G2258A and T597C polymorphisms with pulmonary tuberculosis (PTB) susceptibility are inconsistent. A meta-analysis was conducted to investigate the relationship between TLR2 G2258A and T597C polymorphisms with PTB susceptibility.MethodsA systematic search was performed for published studies on the relationship between TLR2 polymorphisms and PTB susceptibility. Information was gathered from each eligible study, and statistically analyzed.Results6 eligible studies, totaling 1301 cases and 1217 controls on G2258A genotypes, and 8 studies, totaling 2175 cases and 2069 controls on T597C genotypes, were included in the analysis. TLR2 2258G allele and 2258GG genotype were found to be associated with decreased PTB susceptibility (A vs. G: OR = 3.02, 95% CI: 2.22–4.12, P<0.001, GA+AA vs. GG: OR = 2.69, 95% CI = 1.49–4.87, P = 0.001). In the subgroup analyses, the 2258G allele and 2258GG genotype also exhibited a protective effect of PTB risk in Asians (A vs. G: OR = 2.95, 95% CI: 1.91–4.55, P<0.001; GA+AA vs. GG: OR = 3.59, 95% CI: 2.23–5.78, P<0.001), while no associations were observed in Caucasians. No significant associations between T597C polymorphism and PTB were found in the allele model (C vs. T: OR = 0.95, 95% CI: 0.86–1.04, P = 0.28), co-dominant model (CC vs. TT: OR = 0.88, 95% CI = 0.92–1.40, P = 0.25; CT vs. TT: OR = 0.92, 95% CI = 0.80–1.06, P = 0.28), recessive model (CC vs. TT+TC: OR = 0.96, 95% CI: 0.80–1.16, P = 0.69), or dominant model (TC+CC vs. TT: OR = 0.93, 95% CI = 0.76–1.15, P = 0.51). The associations of T597C polymorphism with PTB susceptibility, in the ethnic-specific analyses, were still not significant.ConclusionTLR2 2258G allele may provide protective effects against PTB susceptibility, particularly among Asians, whereas TLR2 T597C polymorphism might not be associated with PTB susceptibility.
Highlights
Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis (M. tuberculosis), leads to a considerable global health burden, especially in Southeast Asia [1]
toll-like receptor 2 (TLR2) 2258G allele and 2258GG genotype were found to be associated with decreased pulmonary tuberculosis (PTB) susceptibility (A vs. G: odds ratios (ORs) = 3.02, 95% CI: 2.22–4.12, P,0.001, GA+AA vs. GG: OR = 2.69, 95% CI = 1.49–4.87, P = 0.001)
The 2258G allele and 2258GG genotype exhibited a protective effect of PTB risk in America (Caucasian) America (Hispanics) Vietnam (Asian) (A vs. G: OR = 2.95, 95% CI: 1.91–4.55, P,0.001; GA+AA vs. GG: OR = 3.59, 95% CI: 2.23–5.78, P,0.001), while no associations were observed in Caucasians
Summary
Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis (M. tuberculosis), leads to a considerable global health burden, especially in Southeast Asia [1]. Only 10% of those who are infected advance to clinical diseases, such as pulmonary tuberculosis (PTB) [2]. The host genetic factors are assumed to play a critical role in tuberculosis pathogenesis, through impact on the gene expression of cytokines and chemokines, which are implicated in the host immune response. Both animal models and segregation analyses have been performed to support the idea of genetic susceptibility to PTB [3,4,5]. Publications regarding the associations of toll-like receptor 2 (TLR2) G2258A and T597C polymorphisms with pulmonary tuberculosis (PTB) susceptibility are inconsistent. A meta-analysis was conducted to investigate the relationship between TLR2 G2258A and T597C polymorphisms with PTB susceptibility
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