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PPARgamma Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

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  • Ulla Vogel, Denmark
  • Stine Segel, Denmark
  • Claus Dethlefsen, Denmark
  • Anne Tjonneland, Denmark
  • Anne Saber, Denmark
  • Hakan Wallin, Denmark
  • Majken Jensen, Denmark
  • Erik Schmidt, Denmark
  • Paal Andersen, Denmark
  • Kim Overvad
  • Kardiologisk Afdeling, Aalborg Sygehus
  • Kardiovaskulært Forskningscenter, Aalborg Sygehus
  • Department of Clinical Epidemiology
  • Klinisk Epidemiologisk Afdeling, Aalborg
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 results in a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between the same polymorphism and factors that modify PPAR activity, such as alcohol intake, smoking, and use of non-steroidal anti-inflammatory medicine (NSAID). METHODS: A case-cohort study including 1034 ACS cases and a sub-cohort of 1666 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 (IRR= 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 (IRR=25.3, CI: 16.5-38.7) compared to homozygous wild type carriers (p for interaction<0.0001). Overall, there were only observed effects 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 effects were due to chance. CONCLUSIONS: In the present study, there were no consistent associations between PPARgamma2 Pro12Ala and risk of ACS, and no consistent interaction with alcohol, BMI, NSAID or smoking in relation to ACS.
Original languageEnglish
JournalB M C Medical Genetics
Volume10
Pages (from-to)52
ISSN1471-2350
DOIs
Publication statusPublished - 2009

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