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NIEHS Researchers Link Gene Variation to Coronary Heart Disease
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NIEHS Researchers Link Gene Variation to Coronary Heart Disease

NIEHS Researchers Link Gene Variation to Coronary Heart Disease
News

NIEHS Researchers Link Gene Variation to Coronary Heart Disease

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Research at the National Institute of Environmental Health Sciences, part of the National Institutes of Health, has 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 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," said Craig Lee, Pharm.D., a researcher at NIEHS and lead author on the study.

"We did not observe the same association in African Americans who had the K55R polymorphism."

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.

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 cardiovascular disease."

"Improved knowledge about the role this gene plays in the onset of cardiovascular disease makes it possible identify people who may be at greater risk, and also to identify individuals who may be more responsive to new drugs that target the enzymes of this metabolic pathway," said Dr. Darryl C. Zeldin, M.D., a Senior Investigator at NIEHS

"We've been studying this pathway in cells and mice for more than a decade, but this study provides the first direct evidence about its importance to coronary heart disease events in humans."

The researchers genotyped 2065 participants for ten known polymorphisms in the "EPHX2" gene.

The researchers were also able to confirm that there was an increased level of enzyme activity in individuals who had the K55R polymorphism.

"By looking at ten different polymorphisms, we were able to survey the gene and determine that this one particular variation is related to cardiovascular disease risk in Caucasians," said Lee.

"More research is needed to determine if this finding is applicable to other populations."

"This study exemplifies the importance of translating basic research findings in the laboratory to clinical studies in humans," said Schwartz.

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