title: 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.
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.
authors.affiliation: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).|Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Dandan
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Liping
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Honghu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4