Evaluation of the association of genetic variants on the chromosomal loci 9p21.3, 6q25.1, and 2q36.3 with angiographically characterized coronary artery disease

Abstract 

Objectives

The chromosomal loci 9p21.3, 6q25.1, and 2q36.3, represented by their respective leading variants rs1333049, rs6922269 and rs2943634, have been linked with a history of coronary artery disease (CAD) by genome-wide association studies. Whereas the association of variant rs1333049 with CAD was analysed in several subsequent studies, replication studies of variants rs6922269 and rs2943634 are missing. Furthermore, no direct association with coronary atherosclerosis has been established. We therefore aimed at investigating the association of the above variants with coronary atherosclerosis.

Methods

We performed genotyping in two large cohorts of consecutive Caucasian patients undergoing coronary angiography for the evaluation of suspected or established stable CAD, comprising 671 and 940 patients, respectively, with a total of 1611 subjects.

Results

In models of dominant inheritance, variant rs1333049 conferred a significantly increased risk of significant coronary stenoses with lumen narrowing ≥50% in both study cohorts, with adjusted odd ratios (OR) of 1.71 (1.15–2.52); p=0.007 and 1.55 (1.10–2.18); p=0.012, respectively. Variant rs6922269 in neither cohort was significantly associated with CAD. Although carriers of the A allele of variant rs2943634 were at an increased risk of significant coronary stenoses in the second cohort (OR=1.41 (1.06–1.88); p=0.018), no such association was found for the first cohort nor for both cohorts combined.

Conclusion

Our data from two populations show that variant rs1333049 is significantly associated with angiographically characterized CAD. In contrast, variant rs6922269 did not show any impact on coronary atherosclerosis. The association between variant rs2943634 and CAD warrants further investigation.

Keywords: Coronary angiography, Coronary artery disease, Single nucleotide polymorphism