Scientists have identified the first DNA sequence variant common in the population that is not only associated with an increased risk of heart failure, but appears to play a role in causing it.
The variant, a change in a single letter of the DNA sequence, impairs channels that control kidney function.
"It's not a heart gene," says Gerald W. Dorn II, MD, the Philip and Sima K. Needleman Professor of Medicine at Washington University School of Medicine in St. Louis and a lead investigator on the study. "It's a kidney gene. This protein is not even expressed in the heart. Nobody has previously considered that kidney-specific gene defects might predispose you to heart failure."
Heart failure is diagnosed when the heart can no longer provide sufficient blood to the body. It can have a number of causes, including high blood pressure, cancer therapy, viral infections of the heart or heart attack.
"It's a syndrome," Dorn says. "You've had sufficient damage to your heart that it doesn't work very well. You collect fluid in your lungs, you swell up, and you have trouble breathing."
The unexpected results highlight the advantage of performing genome-wide studies to find DNA sequence variants associated with disease.
"I was surprised by the finding," says Thomas P. Cappola, MD, assistant professor of medicine at the University of Pennsylvania School of Medicine, also a lead investigator on the study. "This is a good example of how taking unbiased approaches to study human disease can lead you to unexpected targets."
The study, a collaboration between Washington University School of Medicine, the University of Pennsylvania and other institutions, appears Jan. 17 in The Proceedings of the National Academy of Sciences.
In previous work, Dorn and colleagues used a partial genome-wide search technique to define the region of DNA in which sequence changes were associated with heart failure. But mo
|Contact: Joni Westerhouse|
Washington University School of Medicine