Variant on 9p21 strongly associates with coronary heart disease, but lacks association with common stroke

Recently, genome-wide analyses revealed that variants on chromosome 9p21 are associated with myocardial infarction. We investigated whether this association was also present in a Belgian population of coronary artery disease (CAD) patients. As CAD and ischemic cerebrovascular disease (CVD) are thought to share some pathogenic pathways, we further examined the association of 9p21 with this disease. SNP rs10757278 on chromosome 9 was genotyped in 926 patients with CAD from the CAREGENE study, in 648 patients with CVD from the Leuven Stroke Genetics Study (LSGS) and the Belgian Stroke Study (BSS) and in 828 unrelated controls. A systematic review and meta-analysis were carried out in both vascular diseases. The frequency of the risk allele, rs10757278*G, was 55% in CAD cases versus 48% in controls, odds ratio (OR) 1.35 (1.18-1.54), P = 1.3 x 10(-5). No association was found with CVD, OR 1.03 (0.89-1.19), P = 0.73. Meta-analysis revealed a consistent relationship between the risk variant and CAD. However, using a meta- analytic approach in CVD, only a marginal association was observed, which was no longer present after excluding patients with a history of CAD. The risk variant on chromosome 9, tagged by rs10757278, is associated with coronary heart disease in the Belgian population, but not with isolated CVD. These findings suggest different pathogenic mechanisms in CAD versus CVD. European Journal of Human Genetics (2009) 17, 1287-1293; doi: 10.1038/ejhg.2009.42; published online 25 March 2009