Abstract 366: Evidence For Genetic Variations Associated With Increased Risk Of Left Main Disease At Chromosome 9p21
Introduction: Recently, genome-wide association (GWA) studies using ~500.000 SNPs have identified an intergenic region located at chromosome 9p21 which unequivocally conferred substantial risk of myocardial infarction (MI). While MI constitutes the major complication of coronary artery disease (CAD), significant stenosis of the left main coronary artery presents one of the most severe affections of CAD and is associated with an especially poor prognosis. To investigate if genetic variation in 9p21 also affects risk of left main disease we have carried out a comprehensive genetic analysis of this region in 501 affected individuals.
Methods: 501 patients with left main disease and 1,600 controls from the population-based MONICA/KORA Augsburg survey that was conducted as part of the German National Genome Research Network (NGFN) were genotyped for 17 SNPs at 9p21 using the 500K Affymetrix Gene Chip®Array. SNPs fulfilling stringent quality criteria were tested for association with left main disease. The level of significance was adjusted for multiple testing (Bonferroni).
Results: Genotyping results are displayed in table 1⇓.
Conclusion: In striking analogy to recent GWA studies for MI, the large intergenic region located at 9p21 contains numerous SNPs showing highly significant association with left main disease. Our finding in this high-risk population emphasize the crucial impact of this locus on CAD risk.