The influence of polymorphisms related to CCL2 and FCER1A genes on coronary artery stenosis'

Abstract

Cardiovascular disease due to atherosclerosis is the leading cause of morbidity and mortality in the developed world. Atherosclerosis is a complex multifocal arterial disease which involves the interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic polymorphisms significantly influence susceptibility to atherosclerotic vascular diseases. In this project we studied the association of a few pre-selected genetic polymorphisms of CCL2 and FCER1A with coronary atherosclerosis. The protein coded by CCL2, monocyte chemoattractant protein-1 (MCP-1) is important in the initiation of atherosclerosis and crucial in monocyte recruitment into the subendothelial lesions. Since there are conflicting reports on the possible association of the CCL2 rs1024611 polymorphism with coronary artery disease, we investigated the role of this polymorphism. FCER1A influences several inflammatory biomarker levels, including MCP-1 concentrations and may have apotential role in development of cardiovascular disease. The polymorphisms rs2427827 and rs2251746 related to this gene were studied.

This study was conducted on a group of 234 persons who had suspected coronary artery disease.On coronary angiography, 131 individuals were found to have significant coronary arterystenosis, and the remaining 103 individuals had normal coronary arteries or insignificant coronary artery stenosis. The CCL2 rs1024611 polymorphism and FCER1A rs2427827 and rs2251746 polymorphisms were genotyped using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. For the CCL2 rs1024611 polymorphism, there were significant differences between genotype frequencies in the patients with and without significant coronary artery stenosis (p=0.008). For the FCER1A rs2427827 (p=0.31) and rs2251746 (p=0.63) polymorphisms we found no significant differences between the two groups.Our data, from the present study, demonstrate that the CCL2 rs1024611 polymorphism is associated with coronary artery stenosis, whereas the FCER1A rs2427827 and rs2251746 polymorphisms are not.

These findings need to be confirmed in future larger studies, especially in the case of rs1024611, before its usefulness as a marker of risk of the development of atherosclerosis can be advocated.