Association between the TLR4 +896A>G (Asp299Gly) Polymorphism and Asthma: A Systematic Review and Meta-Analysis

Abstract

Objective. To determine whether there is an association between the toll-like receptor 4 (TLR4) +896A>G single nucleotide polymorphism and asthma by conducting a systematic review and meta-analysis. Methods. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search for relevant studies was performed using PubMed (MEDLINE), Scopus, and HuGE Literature Finder databases with additional consultation of the reference lists of included studies. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for the allelic comparison (G vs. A) and the genotypic comparison assuming a dominant genetic model (AG + GG vs. AA). I² statistics were calculated to assess the presence of between-study heterogeneity and funnel plots were inspected for indication of publication bias. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates. Results. Meta-analysis of nine studies consisting of 1838 asthma cases and 1764 controls did not find a significant association between TLR4 +896A>G and asthma (genotypic OR = 1.12, 95% CI: 0.91–1.39, p = .27). Between-study heterogeneity was not detected (I² = 0%) and publication bias was not evident. Sensitivity analysis demonstrated the stability of the null association. Conclusions. The meta-analysis findings suggest a lack of direct association between the TLR4 +896A>G polymorphism and asthma, but gene–environment and gene–gene interaction effects and other considerations involving this polymorphism may exist. Therefore, further study is necessary to fully elucidate the role of TLR4 +896A>G in asthma.

• endotoxin
• gene–environment interaction
• gene–gene interaction
• lipopolysaccharide
• single nucleotide polymorphism
• toll-like receptor 4

Acknowledgment

I thank Linlu Zhao for assisting with the study identification and data extraction process.

Declaration of Interest

The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.