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Promoter Polymorphism of Toll-Like Receptor 4 is Associated with a Decreased Risk of Coronary Artery Disease: A
Dandan Sun1,2, Liping Sun1, Qian Xu1
1Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China (mainland).
Insights
This study found that a specific variation in the Toll-like receptor 4 (TLR4) gene promoter region, rs10116253, is associated with a reduced risk of coronary artery disease (CAD). This genetic factor may influence inflammatory pathways involved in CAD development.
Area of Science:
- Genetics
- Cardiovascular Disease
- Immunology
Background:
- Coronary artery disease (CAD) is a chronic inflammatory condition affecting blood vessels.
- Toll-like receptor 4 (TLR4) plays a role in inflammatory responses.
- Investigating genetic variations in TLR4 could reveal insights into CAD risk.
Purpose of the Study:
- To investigate the association between polymorphisms in the promoter and 3'-untranslated regions (3'-UTR) of the TLR4 gene and the risk of developing CAD.
- To identify specific TLR4 gene variants linked to altered CAD susceptibility.
Main Methods:
- A case-control study involving 424 CAD patients and 424 healthy controls.
- Genotyping of TLR4 polymorphisms (rs10116253, rs10983755, rs11536889) using polymerase chain reaction-restriction fragment length polymorphism.
- Assessment of gene promoter activity using a dual-luciferase reporter assay.
Main Results:
- The TLR4 rs10116253 polymorphism in the promoter region was significantly associated with CAD risk.
- Carriers of variant genotypes (CC+TC) for rs10116253 showed a decreased risk of CAD (OR 0.73).
- This reduced risk was particularly noted in males and individuals younger than 60 years old.
Conclusions:
- The TLR4 rs10116253 polymorphism is linked to a reduced risk of coronary artery disease.
- Genetic variations in TLR4 may modulate inflammatory processes contributing to CAD.
- Further research into TLR4 genetics could inform CAD prevention strategies.
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.
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