title: PPARgamma Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes.
abstract: BACKGROUND
  Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPARgamma2 Pro12Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorphism and factors that modify PPARgamma activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine.
  
  
  METHODS
  A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals.
  
  
  RESULTS
  Homozygous male variant allele carriers of PPARgamma2 Pro12Ala were at higher risk of ACS (HR = 2.12, 95% CI: 1.00-4.48) than homozygous carriers of the Pro-allele. Among men, there was a statistically significant interaction between genotypes and alcohol intake such that homozygous variant allele carriers with a low alcohol intake were at higher risk of ACS (HR = 25.3, CI: 16.5-38.7) compared to homozygous common allele carriers (p for interaction < 0.0001). Overall, the association was only observed among homozygous variant allele carriers. Thus, all the observed associations were obtained in subgroups including small numbers of cases. It is therefore possible that the observed associations were due to chance.
  
  
  CONCLUSIONS
  In the present study, there were no consistent associations between PPARgamma Pro12Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.
authors.affiliation: National Food Institute, Technical University of Denmark, Søborg, Denmark. ulbvo@food.dtu.dk
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Stine
authors.initials: S
authors.lastname: Segel
authors.forename: Claus
authors.initials: C
authors.lastname: Dethlefsen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Anne Thoustrup
authors.initials: AT
authors.lastname: Saber
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
authors.forename: Erik B
authors.initials: EB
authors.lastname: Schmidt
authors.forename: Paal Skytt
authors.initials: PS
authors.lastname: Andersen
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
mesh_terms: D054058:Acute Coronary Syndrome / Q000209:etiology / Q000235:genetics*; D000368:Aged; D000409:Alanine / Q000235:genetics; D000428:Alcohol Drinking / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D016022:Case-Control Studies; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011392:Proline / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047495:PPAR gamma; D011392:Proline; D000409:Alanine