Association of TLR gene polymorphisms with the severity of coronary atherosclerosis in patients with stable coronary artery disease

Abstract

Aim. To investigate the associations of the Toll-like receptor (TLR) gene polymorphisms with the severity of coronary atherosclerosis (CA) estimated by SYNTAX (Systematic Coronary Risk Evaluation) score.
Methods. We recruited 292 patients with stable coronary artery disease (CAD). Genotyping was performed in 96-well format using the TaqMan SNP genotyping assay.
Results. We revealed that the C/C genotype of the rs3804099 polymorphism within the TLR2 gene was significantly associated with severe (SYNTAX ≥23) coronary atherosclerosis (OR=2.03, 95%CI=1.09–3.77, р=0.025). However, there were no statistically significant associations of the TLR1 (rs5743551 and rs5743611), TLR2 (rs5743708), TLR4 (rs4986790 and rs4986791), and TLR6 (rs3775073 and rs5743810) gene polymorphisms with the severity of coronary atherosclerosis. When we performed stepwise logistic regression using 16 clinical risk factors, left ventricular ejection fraction (LVF) <55% and < 2 affected CA were associated with 1.92-fold higher and 6.25-fold lower risk of severe coronary atherosclerosis, respectively, with the area under the ROC curve (AUC) of 0.677 (0.620–0.730). However, when we added all 8 TLR gene polymorphisms into the regression, we found that the C/T genotype of the rs5743551 polymorphism within the TLR1 gene and the A/G genotype of the rs4986790 polymorphism within the TLR4 gene were associated with 1.83-fold higher and 3-fold lower risk of severe coronary atherosclerosis, respectively. Moreover, AUC increased to 0.710 (0.654–0.762).
Conclusion. The C/T genotype within the rs5743551 polymorphism within the TLR1 gene and left ventricular ejection fraction <55% are associated with severe coronary atherosclerosis in patients with stable CAD