Abstract

BACKGROUND: Coronary artery disease (CAD) is considered a chronic inflammatory disease of the blood vessels. Toll-like receptor 4 (TLR4) is a transmembrane receptor involved in inflammatory reactions. The aim of this study was to determine the association between polymorphisms in the promoter region and 3’-untranslated region (3’-UTR) of TLR4, and the associated CAD risk.

MATERIAL AND METHODS: This study enrolled 424 participants with CAD and 424 controls without CAD. The polymorphisms in the promoter region and 3’-UTR of TLR4 were identified from the HapMap database, including rs10116253, rs10983755, and rs11536889. Genomic DNA was extracted from peripheral blood. Polymerase chain reaction-restriction fragment length polymorphism was performed to identify genotype polymorphisms. Relative luciferase activity was measured using the dual-luciferase reporter assay system.

RESULTS: TLR4 rs10116253 in the promoter region was associated with CAD risk. The variant (CC+TC) genotypes of rs10116253 were associated with a decreased CAD risk (OR 95% CI 0.73 (0.54–0.98), p=0.034). In the stratification analyses, the variant (CC+TC) genotypes of rs10116253 were observed to have a relationship with decreased CAD risk in the male subgroup (OR: 95% CI 0.68 (0.48–0.98), p=0.041). Moreover, the variant CC and (CC+TC) genotypes of rs10116253 were correlated with a decreased CAD risk in participants younger than 60-year-old (TC: OR (95% CI 0.62 (0.39–0.98), p=0.042; TC+CC: OR 95% CI 0.63 (0.41–0.98), p=0.039). Regarding rs10116253, the luciferase activity of the mutant C allele construct was lower than that of the wild T allele construct (5.215±0.009 vs. 5.304±0.041; p=0.087).

CONCLUSIONS: The results provided evidence of an association between the TLR4 rs10116253 in the promoter region and a reduced risk of CAD.

Keywords: Coronary Artery Disease, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Toll-Like Receptor 4