The researchers linked the genetic variant to a reduction in the left ventricle's ejection fraction, a measurement cardiologists make of how much blood the heart pumps with each beat. The variant, or polymorphism, involves peroxisome proliferator-activated receptor-alpha (PPAR), a transcription factor that regulates the use of fatty acids within cells.
Transcription factors such as PPAR are proteins that switch on other genes. Scientists have studied PPAR extensively because it is fundamental to cellular metabolism. Most of these studies, however, are in the context of diabetes. The Duke team found that a particular variant of PPAR, a polymorphism called PPAR-I7, is associated with reduced function of the left ventricle.
If additional studies confirm this association between PPAR-I7 and the weakening of the heart's pumping strength, future therapies might be developed to interfere with the molecular pathways that PPAR regulates, the researchers said.
"We found that in a broad sample that PPAR-I7 is associated with lower ejection fractions in heart patients," said Duke cardiologist Mark Donahue, M.D., who presented the results of the Duke analysis Nov. 9, 2004, during the American Heart Association's annual scientific sessions in New Orleans.
"Furthermore, we found that this adverse association is additive," Donahue continued. "Inheriting the polymorphism from one parent is bad, and inheriting it from both parents is even worse. The results of our analysis suggest that the PPAR signaling pathway in
Contact: Richard Merritt
Duke University Medical Center