Association of TLR and TREM-1 gene polymorphisms with risk of coronary artery disease in a Russian population

Abstract

Atherosclerosis, manifesting itself as acute coronary syndrome, stroke, and peripheral arterial diseases, is a chronic progressive inflammatory disease which is driven by responses of both innate and adaptive immunity. Toll-like receptors (TLRs) and Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) are important effectors of the innate immune system, and polymorphisms within genes encoding them may increase risk of occurrence of various pathologies including cardiovascular disorders. Thus, we carried out a genetic association study on the sample of 702 consecutive Caucasian (Russian) patients with coronary artery disease (CAD) and 300 age-, sex-, and ethnicity-matched healthy controls. We revealed that the C/C genotype of the TLR1 rs5743551 polymorphism was significantly associated with a reduced risk of CAD according to the recessive model (OR=0.41, 95% CI=0.20-0.84, P=0.017, adjusted by age and gender). Concerning TREM-1 gene polymorphisms, we found that A/A genotype of the rs2234237 polymorphism, the G/G genotype of the rs6910730 polymorphism, the C/C genotype of the rs9471535 polymorphism, and the T/T genotype of the rs4711668 polymorphism were significantly associated with elevated CAD risk according to the recessive model (OR=5.52, 95% CI=1.17-25.98, P=0.011; OR=4.28, 95% CI=1.09-16.81, P=0.021; OR=5.55, 95% CI=1.18-26.09, P=0.011, and OR=1.66, 95% CI=1.10-2.52, P=0.014, respectively, adjusted by age and gender). Conversely, the G allele of the rs1817537 polymorphism, the T allele of the rs2234246 polymorphism, and the T allele of the rs3804277 polymorphism significantly correlated with similarly decreased risk of CAD according to the dominant model (OR=0.57, 95% CI=0.40-0.81, P=0.0013; OR=0.59, 95% CI=0.42-0.84, P=0.003, and OR=0.58, 95% CI=0.41-0.81, P=0.0014, respectively, adjusted by age and gender). We conclude that certain TLR and TREM-1 gene polymorphisms may be associated with CAD in Russian population; however, their significance as predictive and pathogenic markers of CAD should be interpreted with caution in other populations.

Keywords: Atherosclerosis; Coronary artery disease; Gene polymorphisms; Immunity; Toll-like receptors; Triggering Receptor Expressed on Myeloid Cells-1.