Association between PPAR-alpha gene polymorphisms and myocardial infarction
Résumé
Peroxisome proliferator activated receptor alpha (PPAR{eta}) regulates the expression of genes that are involved in lipid metabolism, tissue homeostasis, and inflammation. Consistent rodent and human studies suggest a link between PPAR{eta} function and cardiovascular disease, qualifying PPAR {eta} as a candidate gene for coronary artery disease. We comprehensively evaluated common genetic variations within the PPAR {eta} gene and assessed their association with myocardial infarction. First, we characterized the linkage disequilibrium within the PPAR {eta} gene in an initial case-control sample of 806 individuals from the Regensburg Myocardial Infarction Family Study using a panel of densely spaced single nucleotide polymorphisms (SNPs) across the gene. Single SNP analysis showed significant association with the disease phenotype (OR=0.74, P=0.012, 95% CI=0.61-0.94 for rs135551). Moreover, we identified a protective 3-marker haplotype with an association trend for myocardial infarction (OR=0.76, P=0.067, 95% CI=0.56-1.92). Subsequently, we were able to confirm the single SNP and haplotype association results in an independent second case-control cohort with 667 cases from the Regensburg Myocardial Infarction Family Study and 862 control individuals from the WHO MONICA Augsburg project (OR=0.87, P=0.046, 95% CI=0.72-0.99 for rs135551; OR=0.80, P=0.034, 95% CI=0.65-0.98 for the 3-marker haplotype, respectively). From these cross-sectional association results, we provide evidence that common variations in the PPAR {eta} gene may influence the risk of myocardial infarction in a European population.
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