Association between PPARalpha gene polymorphisms and myocardial infarction.
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.
Reinhard
Wibke
W
Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany.
Stark
Klaus
K
Sedlacek
Kamil
K
Fischer
Marcus
M
Baessler
Andrea
A
Neureuther
Katharina
K
Weber
Stefan
S
Kaess
Bernhard
B
Wiedmann
Silke
S
Mitsching
Stefan
S
Lieb
Wolfgang
W
Erdmann
Jeanette
J
Meisinger
Christa
C
Doering
Angela
A
Tolle
Ralf
R
Jeron
Andreas
A
Riegger
Guenter
G
Hengstenberg
Christian
C
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
D047493:PPAR alpha