Abstract 12760: Identification of a Novel Susceptibility Locus on Chromosome 12 With the First Genome-Wide Association Study on Coronary Restenosis
Purpose - Percutaneous Coronary Intervention (PCI) is the most important treatment modality for coronary revascularization. Despite all advances over the recent years, restenosis still remains an important complication of PCI. Risk stratification might enable individualized treatment. Genetic factor are known to influence the risk of restenosis and could therefore be useful in identifying patients at risk. Moreover, identification of genetic markers for restenosis might aid to our understanding of the mechanistic insights of restenosis. With this purpose we conducted a Genome Wide Association Study (GWAS) in the GENetic Determinants of Restenosis (GENDER) study.
Methods - GENDER is a multicentre follow-up study and was designed to investigate the association of genetic variation and clinical restenosis. A GWAS was performed in a subpopulation of GENDER (295 cases and 571 controls) using the Illumina 610K array. The most significant SNPs were replicated in three independent case-control populations (533 cases and 3067 controls). Furthermore, as a validation of involvement of these SNPs in coronary artery disease (CAD), the association with mortality and CAD events was investigated in GENDER as well as in the PROSPER study, a statin trial consisting of 5804 elderly patients with an increased risk of CAD.
Results - Two SNPs in an intergenic region on chromosome 12 associated with clinical restenosis were identified. These two SNPs were replicated in the replication cohort under a recessive model of heredity. The combined p-value of the all studies was 1.11E-7. The SNPs were also associated with the risk of all-cause mortality in GENDER (p=0.005). In the PROSPER study significant associations were found with the occurrence of coronary events (p=0.005) as well as with all-cause mortality (p=0.007).
Conclusions - We present the results of the first GWAS in a large prospective restenosis cohort. We have found a novel susceptibility locus for restenosis at chromosome 12 which could be involved in regulatory functions of neighbouring genes as stabiline2 (STAB2) or NT5DC3. The concurrent association with cardiovascular events and all-cause mortality might implicate a more general role of this locus in the development of coronary artery diseases.
- © 2011 by American Heart Association, Inc.