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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. CONCLUSION: 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.

SUBMITTER: Vogel U

PROVIDER: S-EPMC2698834 | biostudies-other | 2009

REPOSITORIES: biostudies-other

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

Vogel Ulla U Segel Stine S Dethlefsen Claus C Tjønneland Anne A Saber Anne Thoustrup AT Wallin Håkan H Jensen Majken K MK Schmidt Erik B EB Andersen Paal Skytt PS Overvad Kim K

BMC medical genetics 20090607

<h4>Background</h4>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 ...[more]

PMID: 19500413

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Project description:ObjectiveTo develop a clinical risk prediction tool for estimating the cumulative six month risk of death and death or myocardial infarction to facilitate triage and management of patients with acute coronary syndrome.DesignProspective multinational observational study in which we used multivariable regression to develop a final predictive model, with prospective and external validation.SettingNinety four hospitals in 14 countries in Europe, North and South America, Australia, and New Zealand.Population43,810 patients (21,688 in derivation set; 22,122 in validation set) presenting with acute coronary syndrome with or without ST segment elevation enrolled in the global registry of acute coronary events (GRACE) study between April 1999 and September 2005.Main outcome measuresDeath and myocardial infarction.Results1989 patients died in hospital, 1466 died between discharge and six month follow-up, and 2793 sustained a new non-fatal myocardial infarction. Nine factors independently predicted death and the combined end point of death or myocardial infarction in the period from admission to six months after discharge: age, development (or history) of heart failure, peripheral vascular disease, systolic blood pressure, Killip class, initial serum creatinine concentration, elevated initial cardiac markers, cardiac arrest on admission, and ST segment deviation. The simplified model was robust, with prospectively validated C-statistics of 0.81 for predicting death and 0.73 for death or myocardial infarction from admission to six months after discharge. The external applicability of the model was validated in the dataset from GUSTO IIb (global use of strategies to open occluded coronary arteries).ConclusionsThis risk prediction tool uses readily identifiable variables to provide robust prediction of the cumulative six month risk of death or myocardial infarction. It is a rapid and widely applicable method for assessing cardiovascular risk to complement clinical assessment and can guide patient triage and management across the spectrum of patients with acute coronary syndrome.

Dataset Information

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

Publications

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

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