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Common gene variant increases risk of atherosclerosis

version, known as KL-VS, while another 25 percent carry one "bad" copy.

"While KL-VS may increase the risk of dying early, this new study suggests that it's possible to modify that risk by making lifestyle changes, which makes the possibility of genetic testing worth considering," says Dietz, who adds that no test is commercially available at this time.

Japanese scientists were the first to learn that variations in klotho, named after the Greek Fate purported to spin the thread of life, made mice age quickly and similarly to humans, developing conditions similar to atherosclerosis and osteoporosis that are practically unheard of in the furry critters.

Intrigued, Dietz and his colleagues, including Dan Arking, Ph.D., now a postdoctoral fellow, determined that KL-VS was more common in people who die before the age of 65. Searching for an explanation of how klotho could reduce life expectancy, the researchers turned to two Hopkins studies originally designed to check for undetected atherosclerosis in apparently healthy siblings of people hospitalized for cardiovascular disease before the age of 60.

More than 900 people between the ages of 39 and 59 were included in the new analysis. The scientists determined which klotho variants each participant had, and linked that to the person's clinical diagnosis and risk factors, which had been gathered as part of the older studies.

One of these studies, called SIBS-I, included 520 apparently healthy siblings of hospitalized patients, and 97 of them were discovered to have undetected atherosclerosis. The other, called SIBS-II, included only African Americans and found that 56 of 436 participants had undetected atherosclerosis.

For the SIBS-I group, roughly 15 percent of the 373 participants with two "good" copies of klotho had undetected atherosclerosis. Of the 135 people with one copy of the KL-VS version of klotho, about 25 percent had hidden coronary artery disease, a
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
1-May-2003


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