Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms in type 2 diabetes mellitus: A meta-analysis of 15,059 subjects

• We performed a meta-analysis to derive a more precise estimation of the relationship.
• Our study has the potential to detect small effects in genetic association studies.
• Our study suggests that TLR4 gene polymorphisms are not associated with T2DM risk.

AimsToll-like receptor 4 (TLR4) gene Asp299Gly and Thr399Ile polymorphisms have been reported to be associated with susceptibility to type 2 diabetes mellitus (T2DM) with inconsistent results. In an effort to clarify earlier inconclusive results, a meta-analysis evaluating the precise associations between TLR4 gene Asp299Gly and Thr399Ile polymorphisms and T2DM risk was performed.MethodsWe searched the PubMed, Embase, Web of Science, CBMdisc, CNKI, and Google Scholar until July 17, 2014. Additionally, hand searching of the references of identified articles were performed. Original observational studies dealing with the associations between TLR4 gene Asp299Gly and Thr399Ile polymorphisms and T2DM risk were selected. Heterogeneity and publication bias were determined and the meta-analysis was performed by Review Manager 5.1.4 and Stata 11.0.ResultsSeventeen articles involving 25 studies were included in the final meta-analysis, covering a total of 5963 T2DM cases and 9096 controls. For TLR4 gene Asp299Gly polymorphism, 17 studies were combined showing no evidence for association between TLR4 gene Asp299Gly polymorphism and T2DM risk. For TLR4 gene Thr399Ile polymorphism, eight studies were combined. There was also lack of evidence for significant association between TLR4 gene Thr399Ile polymorphism and T2DM risk. In addition, the similar results were obtained in the sensitivity analyses.ConclusionsThe present meta-analysis indicates that TLR4 gene Asp299Gly and Thr399Ile polymorphisms are not associated with increased T2DM risk.