Associations between genetic variants and angiographic characteristics in patients with coronary artery disease

Aim: In this study, we investigated the genetic determinants of lesion characteristics and the severity of coronary artery disease (CAD. using a genome-wide association study (GWAS. and replication genotyping. Methods: The discovery set for GWAS consisted of 667 patients exhibiting angiographically diagnosed CAD with symptoms. For replication genotyping, 837 age-and sex-matched CAD patients were selected. Genetic determinants of lesion characteristics (diffuse vs. non-diffuse lesions), the number of diseased vessels (multi-vessel vs. single vessel disease. and the modified Duke score (high vs. low), which indicates the severity of CAD, were analyzed after adjusting for confounding factors. Results: Single nucleotide polymorphisms (SNPs. rs12917449, rs10152898 and rs231150 were associated with diffuse lesions, while rs1225006 and rs6745588 were associated with multi-vessel disease. However, on replication genotyping, no significant associations were found between any of these five SNPs and the lesion characteristics or CAD severity. In contrast, in the combined population of both the discovery and replication sets, genotypes rs125006 of CPNE4 and rs231150 of TRPS1 were found to be significantly associated with the modified Duke score. The addition of rs1225006 to conventional risk factors had significant incremental value in the model of the score. Conclusions: The associations between five SNPs identified using GWAS and angiographic characteristics were not significant in the current replication study. However, two variants, particularly rs1225006, were found to be associated with the severity of CAD in the combined set. These results indicate the potential clinical implication of these variants with respect to the risk of CAD.