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NIEHS researchers link gene variation to coronary heart disease

New research at the National Institute of Environmental Health Sciences, part of the National Institutes of Health, found that a common genetic variation makes some people more susceptible to coronary heart disease (CHD). Caucasians who carry this gene variation are approximately 1.5 times more likely to have a CHD event, such as a heart attack, than those who do not have the gene variation. Gene variations are also known as polymorphisms. About 15 percent of all Caucasians have this particular polymorphism.

"We found that Caucasians who carry this polymorphism, named K55R, were at significantly higher risk of coronary heart disease, independent of other risk factors, like cigarette smoking, diabetes, and hypertension. We did not observe the same association in African Americans who had the K55R polymorphism," said Craig Lee, Pharm.D., a researcher at NIEHS and lead author on the study. The study is published in the Volume 15, No. 10 issue of Human Molecular Genetics.

This research showed that Caucasians with the K55R polymorphism had an accelerated break down of beneficial fatty acids called epoxyeicosatrienoic acids or EETs, which are known to play a protective role in the cardiovascular system. These fatty acids help to lower blood pressure, prevent blood clotting and fight inflammation.

The K55R polymorphism is a naturally-occurring, inherited variation of EPHX2--the epoxide hydrolase gene. EPHX2 generates an enzyme that rids the body of beneficial EET fatty acids, as part of normal human metabolism. In people with the K55R polymorphism, this normal process is accelerated and even more of the protective EETs are lost.

"This research builds on a body of evidence suggesting the importance of this gene and its fatty acid products in the cardiovascular system," said David A. Schwartz, M.D., NIEHS Director. "It also suggests that this metabolic pathway may serve as a useful target for the prevention or treatment of cardiovascu
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Contact: Robin Mackar
rmackar@niehs.nih.gov
919-541-0073
NIH/National Institute of Environmental Health Sciences
11-May-2006


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