Risk polymorphism at 9p21.3 predicts severity of coronary artery disease in Caucasian men

Abstract

Coronary artery disease (CAD) is the leading cause of premature death in developed countries and emerging risk in developing nations. CAD is multifactorial condition where genetics, lifestyle and environment all contribute to its development. The 9p21.3 locus is associated with CAD in multiple studies and in multiple populations. Despite of many replications, mechanism how 9p21.3 contributes to CAD is still unclear. Our aim was to investigate role of 9p21.3 in severity of CAD. This was the study of 492 angina patients that have undergone coronary angiography. They were enrolled from Latvian Centre of Cardiology at Pauls Stradins Clinical University Hospital from 2006 to 2008 and were genotyped for single SNP at 9p21.3 locus - rs1333049 using TaqMan genotyping assay and researchers carrying out genotyping were unaware of angiography results. Association between rs1333049 risk allele and number of coronary arteries with 50% stenosis, number of coronary arteries with 75% stenosis and one coronary vessel disease and three coronary vessel disease (>75% stenosis in one and three and more coronary arteries respectively) was assessed. Results showed that rs1333049 risk allele C was associated with three vessel disease (OR = 1.45, p = 0.01, adjusted for genre, age, smoking status and BMI) however no association was found with one vessel disease or number of coronary arteries with severe stenosis. Genre stratified analysis showed that allele C is associated with three vessel disease in men (n = 392, OR = 1.71, p = 0.001, adjusted for genre, age, smoking status and BMI) but not in women (n = 100, OR = 1.27, p = 0.47). Conclusion: Common SNP risk allele predicts severity of coronary artery disease in men, but not women.