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First link found in humans between common gene and artery-clogging disease

LOS ANGELES (Jan. 1) - Scientists have found the first strong link in humans between a common gene and risk for the disease that leads to most heart attacks and strokes, according to results of a study by researchers at the Keck School of Medicine of the University of Southern California and the David Geffen School of Medicine at UCLA.

People with a variant form of a gene called 5-lipoxygenase (ALOX5) have a greater risk of atherosclerosis, a build-up of cholesterol in artery walls that contributes to heart disease, scientists report in the Jan. 1 issue of the New England Journal of Medicine. The high-risk form of ALOX5 occurred in about 5 percent of participants in the Los Angeles Atherosclerosis Study, which follows the cardiovascular health of 470 utility workers in Southern California.

Researchers have known for many years that atherosclerosis risk may run in families, yet the genetic markers known to increase risk for atherosclerosis either were rare or made only a slight difference. This new finding, however, indicates that a substantial proportion of people carry a form of ALOX5 that may wield potent effects on cardiovascular disease.

"One of the most interesting aspects of this new finding is that the effect of the ALOX5 gene on atherosclerosis depends upon diet," says co-author James Dwyer, Ph.D., professor of preventive medicine at the Keck School of Medicine of USC and the Los Angeles Atherosclerosis Study's principal investigator. "The adverse effect of this gene is increased by dietary intake of certain n-6 polyunsaturated fats, while the adverse effect is blocked by intake of fish oils containing n-3 polyunsaturated fatty acids."

For those who carry a high-risk form of ALOX5, the "bad" fats are two n-6 polyunsaturated fats called arachidonic acid and linoleic acid. Arachidonic acid is found in some meats, while linoleic acid is found in many vegetable oils. The "good" fats for this group are n-3 (or omega-
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Contact: Jon Weiner
jonweine@usc.edu
213-215-4655
University of Southern California
31-Dec-2003


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