Key result
The rs135551 polymorphism in the PPARalpha gene was significantly associated with a reduced risk of myocardial infarction (OR 0.74; 95% CI 0.61-0.94; P=0.012), confirmed in an independent cohort.
Why the study?
Do common variations in the PPARalpha gene influence the risk of myocardial infarction in a European population?
Case-Control (n=2,335)
Yes
Do common variations in the PPARalpha gene influence the risk of myocardial infarction in a European population?
Odds Ratio: 0.74 (95% CI 0.61–0.94)
p-value: p=0.012
Common genetic variations in the PPARalpha gene, specifically the rs135551 polymorphism and a three-marker haplotype, are associated with a reduced risk of myocardial infarction.
Does not support clinical genetic testing for MI risk; leaves open validation in prospective cohorts.
PPARalpha (peroxisome-proliferator-activated receptor alpha) regulates the expression of genes that are involved in lipid metabolism, tissue homoeostasis and inflammation. Consistent rodent and human studies suggest a link between PPARalpha function and cardiovascular disease, qualifying PPARalpha [PPARA in HUGO (Human Genome Organisation) gene nomenclature] as a candidate gene for coronary artery disease. In the present study, we comprehensively evaluated common genetic variations within the PPARalpha gene and assessed their association with myocardial infarction. First, we characterized the linkage disequilibrium within the PPARalpha gene in an initial case-control sample of 806 individuals from the Regensburg Myocardial Infarction Family Study using a panel of densely spaced SNPs (single nucleotide polymorphisms) across the gene. Single SNP analysis showed significant association with the disease phenotype [OR (odds ratio)=0.74, P=0.012, 95% CI (confidence interval)=0.61-0.94 for rs135551]. Moreover, we identified a protective three-marker haplotype with an association trend for myocardial infarction (OR=0.76, P=0.067, 95% CI=0.56-1.02). 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 (World Health Organization) MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg project (OR=0.87, P=0.046, 95% CI=0.72-0.99 for rs135551 and OR=0.80, P=0.034, 95% CI=0.65-0.98 for the three-marker haplotype respectively). From these cross-sectional association results, we provide evidence that common variations in the PPARalpha gene may influence the risk of myocardial infarction in a European population.
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Reinhard et al. (2008) conducted a case-control in Myocardial infarction (n=2,335). PPARalpha gene polymorphisms (rs135551) vs. Reference genotype was evaluated on Myocardial infarction (OR 0.74, 95% CI 0.61-0.94, p=0.012). The rs135551 polymorphism in the PPARalpha gene was significantly associated with a reduced risk of myocardial infarction (OR 0.74; 95% CI 0.61-0.94; P=0.012), confirmed in an independent cohort.
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