Promoter Polymorphism of Toll-Like Receptor 4 is Associated with a Decreased Risk of Coronary Artery Disease: A Case-Control Study in the Chinese Han Population
Dandan Sun, Liping Sun, Qian Xu, Honghu Wang, Jun Yang, Yuan Yuan
Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland)
Med Sci Monit 2017; 23:276-284
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