Significant role of ADRB3 rs4994 towards the development of coronary artery disease

Abstract

Coronary artery disease (CAD) is the most common type of heart disease and cause of heart attacks. It has been proposed that both the susceptibility to disease and the interindividual variability in response to treatment relates in part to genetic polymorphisms, particularly those polymorphisms for neurotransmitter and drug receptors. Common functional polymorphisms in β-adrenergic receptor genes (ADRB) have been associated with heart failure phenotypes. Therefore, the purpose of the present study was to explore the association of genetic variants in ADRB3 (C190T or Trp64Arg) ADRB1 (C1165G or Arg389Gly), and ADRA2A (C-1291G) with CAD. The present study recruited a total of 600 consecutive patients with angiographically confirmed CAD and 200 population-matched controls (173 men and 27 women) (mean age 54.10±8.30 years). The ADRB3 T190C, ADRA2A C-1291G, and ADRB1 C1165G polymorphisms were determined by PCR-restriction fragment length polymorphism. The putative functional effects were determined in the coding region of the ADRD3 gene by online web servers FASTSNP and F-SNP. On comparing the genotype frequency distribution in CAD patients with that of healthy individuals, significant association was observed with the CC genotype of the ADRB3 T190C polymorphism (P=0.040, odds ratio=1.5). Also, at the allelic level the C allele of ADRB3 T190C conferred risk for CAD (P=0.005, odds ratio=1.7). The ADRA2A C-1291G and ADRB1 C1165G polymorphisms were not found to be a risk for CAD when compared with controls. The present study finding suggests that ADRB3 C190T may also be involved in the complex pathophysiology of CAD.