|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 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.
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 cardiovascular
“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, who is also an author on the study. “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
Coronary heart disease is a major public health problem, with approximately
1.2 million Americans estimated to experience a CHD event this year. Researchers
report some preliminary findings showing that people who smoked and carried K55R
gene variation were at the highest risk for CHD.
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.”
Participants of this study were part of a larger study, the Atherosclerosis
Risk in Communities (ARIC) Study, which is funded by the National Heart, Lung,
and Blood Institute. The ARIC Study is a long-term study consisting of nearly
16,000 men and women age 45-64 from four diverse communities, including Forsyth
County, NC; Jackson, MS; Minneapolis, MN; and Washington County, MD. The study,
which started in 1987, seeks to investigate and identify cardiovascular disease
risk factors in men and women.
“This study exemplifies the importance of translating basic research findings
in the laboratory to clinical studies in humans” said Schwartz.
The National Institute of Environmental Health Sciences (NIEHS), a component
of the National Institutes of Health, supports research to understand the effects
of the environment on human health. For more information on environmental health
topics, please visit our website at http://www.niehs.nih.gov/.
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Agency — includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit www.nih.gov.