title: Association between PPARalpha gene polymorphisms and myocardial infarction.
abstract: 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.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany.
authors.forename: Wibke
authors.initials: W
authors.lastname: Reinhard
authors.forename: Klaus
authors.initials: K
authors.lastname: Stark
authors.forename: Kamil
authors.initials: K
authors.lastname: Sedlacek
authors.forename: Marcus
authors.initials: M
authors.lastname: Fischer
authors.forename: Andrea
authors.initials: A
authors.lastname: Baessler
authors.forename: Katharina
authors.initials: K
authors.lastname: Neureuther
authors.forename: Stefan
authors.initials: S
authors.lastname: Weber
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kaess
authors.forename: Silke
authors.initials: S
authors.lastname: Wiedmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Mitsching
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: Angela
authors.initials: A
authors.lastname: Doering
authors.forename: Ralf
authors.initials: R
authors.lastname: Tolle
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeron
authors.forename: Guenter
authors.initials: G
authors.lastname: Riegger
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000886:Anthropometry / Q000379:methods; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D047493:PPAR alpha / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D047493:PPAR alpha