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Antioxidant gene mutation gives free radicals free reign

HONOLULU, April 25 A gene mutation for a molecule that helps the body ward off free radicals almost doubles the risk of developing atherosclerotic heart or brain vessel disease, according to a study presented today at the American Heart Associations Asia Pacific Scientific Forum.

Our study shows that even people without conventional cardiovascular risk factors (e.g., cholesterol, hypertension, smoking, etc.) may be genetically predisposed to develop atherosclerosis. The study points to one such genetic risk factor that is relatively common in the general population. Biologically, our findings make sense and could suggest a potential new target for anti-atherosclerotic drug therapy, says the studys lead author, Klaus Juul, M.D., research fellow, department of clinical biochemistry, Herlev University Hospital, Herlev, Denmark.

Free radicals are molecules missing an electron. When the free radicals encounter cells, they make them unstable, which may kill them.

When free radicals combine with low-density lipoprotein, they turn it into oxidized LDL, which is more dangerous because it is likely to form plaque in the blood vessel wall.

Oxidation, a naturally occurring chemical process, has been thought to promote the development of atherosclerosis. However, little is known about hereditary causes of increased oxidation, called oxidative stress, he says.

Researchers have already identified an enzyme called extracellular superoxide dismutase that counteracts oxidation. They found that a mutation in the gene called Arg213Gly that encodes the enzyme was associated with a 10-fold increase in the amount of the substance in the blood plasma. They suspected that the increase in the plasma meant that the enzyme was lost from the blood vessels and tissues, and instead pooled in the blood.

Carriers of the mutation may therefore lack the natural defense mechanisms against oxidation at the very place where these defenses are most needed. We want
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Contact: Carole Bullock
carole.bullock@heart.org
214-706-1279
American Heart Association
25-Apr-2002


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