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California Team Links Mutation, Diet With Increased Risk of Cardiovascular Disease


Researchers in California said they have found a “strong link” between a genetic mutation and certain cardiovascular diseases. Their research also showed that “a substantial proportion” of individuals carry the mutant form of the gene, called 5-lipoxygenase, and that diet may influence disease progression.

Results of their research, if validated, may be used as genetic markers in molecular diagnostics for cardiovascular disease, especially atherosclerosis.

To be sure, scientists have known for some time that the risk of developing atherosclerosis may run in families, though the genetic markers implicated in this elevated risk are either rare or made only a slight difference in the development of the disease.

Yet these new findings, made by a team of researchers from the Keck School of Medicine of the University of Southern California and the David Geffen School of Medicine at UCLA, suggest that a “substantial proportion” of people carry the mutated gene, and that at least one version of the gene, which is also known as ALOX5, contributes to a “greater risk” of disease. To arrive at its results, which appear in the Jan. 1 issue of the New England Journal of Medicine, the team examined 470 healthy middle-aged men and women. The researchers recorded each participant’s diet over 18 months and used ultrasound to measure the thickness of carotid artery walls in each patient. The team also examined the ALOX5 gene from each participant to determine whether it was a wild-type or mutant form.

The researchers found that arterial intima were as much as 18 percent thicker in individuals who did not have the wild-type ALOX5 gene. They also discovered that arterial walls “thickened faster” among individuals with a “high-risk version” of the gene, and among those who ate greater amounts of food containing n-6 polyunsaturated fatty acids. The researchers also noticed that a diet high in n-3 polyunsaturated fatty acids “seemed to protect” patients from developing certain cardiovascular diseases.

The results suggest that people with a high-risk form of the ALOX5 gene “could reduce their risk by eating less n-6 polyunsaturated fats and more n-3 polyunsaturated fatty acids.” In the rest of the population, eating these fatty acids seems to have little impact on atherosclerosis, James Dwyer, a co-author of the study and a professor of preventive medicine at the Keck School of Medicine of USC and the Los Angeles Atherosclerosis Study’s principal investigator. However, “there is substantial evidence that consuming a lot of n-3 fatty acids from fish oils prevents arrhythmias involved in sudden cardiac death,” the team wrote.

“One of the most interesting aspects of this new finding is that the effect of the ALOX5 gene on atherosclerosis depends upon diet,” Dwyer said in a statement. “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.”

Hooman Allayee, a study co-author and a human genetics researcher at the David Geffen School of Medicine at UCLA, said in a statement that earlier research linked the ALOX5 gene to asthma, “so physicians might potentially prescribe existing asthma medications to prevent and control atherosclerosis in those genetically at high risk.”

— KL

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