The PPARGC1A Gly482Ser polymorphism is associated with left ventricular diastolic dysfunction in men.

Abstract

BACKGROUND:

The Gly482Ser polymorphism in peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) has been demonstrated to be associated with diabetes, obesity and hypertension, all of which are important risk factors for left ventricular diastolic dysfunction.

METHODS:

The PPARGC1A Gly482Ser polymorphism was genotyped in a community-based cohort of 499 men and 533 women, who also underwent an echocardiographic examination to determine their left ventricular diastolic function. The association between the polymorphism and the presence of diastolic dysfunction was evaluated using logistic regression models.

RESULTS:

The Ser allele of the PPARGC1A Gly482Ser polymorphism was significantly associated with a lower risk of diastolic dysfunction in men, but not in women. In a model adjusting for potential confounders (age, body mass index, leisure time physical activity, hypertension and diabetes) the results were still significant and substantial (odds ratio 0.13, 95% confidence interval 0.03-0.54, p for trend = 0.004). The results were consistent in a series of models, and they imply a multiplicative, protective effect of the Ser allele, with lower risk of diastolic dysfunction for each copy of the allele.

CONCLUSION:

The Ser allele of the PPARGC1A Gly482Ser polymorphism was associated with decreased risk of diastolic left ventricular dysfunction in men, but not in women, in our large community-based sample. It was associated with a substantially decreased risk, even after adjustment for potential confounders. The clinical importance of the findings has to be established in further studies.

• Authors: Erik Ingelsson, Louise Bennet, Martin Ridderstråle, Marianne Söderström, Lennart Råstam, Ulf Lindblad
• Journal: BMC cardiovascular disorders (BMC Cardiovasc Disord) Vol. 8 Pg. 37 (Dec 11 2008) ISSN: 1471-2261 [Electronic] England
• PMID: 19077249 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heat-Shock Proteins
• PPARGC1A protein, human
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Transcription Factors
• Serine
• Glycine

Topics

• Adult
• Aged
• Alleles
• Cohort Studies
• Female
• Glycine (genetics)
• Heat-Shock Proteins (genetics)
• Humans
• Male
• Middle Aged
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Polymorphism, Genetic (genetics)
• Serine (genetics)
• Sex Characteristics
• Transcription Factors (genetics)
• Ventricular Dysfunction, Left (epidemiology, genetics)