Lack of association between TLR4 Asp299Gly polymorphism and atherosclerosis: evidence from meta-analysis

Introduction: Toll like receptor 4 (TLR4) expression was found to increase markedly in human atherosclerotic lesions, notably on macrophages and endothelial cells. TLR4 Asp299Gly polymorphism was associated with a blunted receptor activity and a subsequently diminished inflammatory response, and may subsequently reduce atherosclerosis (AS) risk. However, the results of molecular epidemiological studies remained inconsistent.

Materials and methods: The PubMed, CNKI databases were searched for all articles available. The OR corresponding to the 95% confidence interval (95% CI) was used to assess the association between TLR4 Asp299Gly polymorphism and risk of AS.

Results: 15 case-control studies with 9,989 cases and 6,746 controls were available for this analysis. For control subjects, G allele frequency of TLR4 Asp299Gly polymorphism was ranging from 0.045 to 0.085. The G allele and the AG/GG genotypes were not associated with significantly risk of AS (OR=1.02, 95% CI=0.83 - 1.26 for G versus A and OR=0.96, 95% CI=0.80 - 1.15 for AG/GG versus AA, respectively) by random effects model.

Conclusion: These findings indicated that TLR4 Asp299Gly polymorphism may not play a role in AS development.