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Common gene variant increases risk of atherosclerosis

A common version of a gene has been identified as a potent risk factor for early-onset atherosclerosis, report the Johns Hopkins scientists who first linked it to shorter life expectancy in humans. Their report appears in the May issue of the American Journal of Human Genetics.

Using information and samples from two earlier studies of people at high risk for heart disease, the team discovered that those with at least one copy of a specific version of this gene, called "klotho," are almost twice as likely to have undetected atherosclerosis than others. Startlingly, smokers with low amounts of "good" cholesterol had 10-fold greater risk if they also had this gene variant.

"If you knew you had this version of klotho, should you keep smoking? Should you exercise more? Eat better? Lose weight?" asks Hal Dietz, M.D., a Howard Hughes Medical Institute associate investigator and professor of pediatrics and molecular biology and genetics at Johns Hopkins. "This gene variant appears to be a potent risk factor for atherosclerosis.

"You have to be very careful with association-type studies like ours, but what we've seen here is not a subtle trend but a strong observation in two independent study populations," adds Dietz, also a member of Hopkins' McKusick-Nathans Institute for Genetic Medicine.

Atherosclerosis, or so-called hardening of the arteries, is a key risk factor for heart attack and stroke, two of the nation's top killers. Lifestyle changes, such as eating a healthier diet, quitting smoking, exercising more and taking certain drugs, can lower the risk of heart disease and death by reducing cholesterol levels and weight.

Everyone has two copies of the klotho gene (one inherited from each parent), but last year the Hopkins researchers found that, of several common versions of klotho, one was associated with earlier death from all causes. Moreover, they showed that roughly 2.5 percent of the population has two copies of this "bad"
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
1-May-2003


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