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 Association’s 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 study’s 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 wanted to investigate if this defect is a risk factor for the development of atherosclerosis in heart or brain vessels. Atherosclerosis leads to heart attacks and strokes, which are responsible for about 40 percent of all deaths in Western societies,” says Juul. “If the carriers of this mutation have a reduced antioxidative defense in the blood vessels, they might be more prone to heart or brain disease.”
Researchers had already known that 2 percent to 3 percent of the Danish general population have inherited a defect in this gene from their parents. (This statistic can be extrapolated to indicate about six million U.S. residents). The researchers wanted to test the theory that carriers would have an increased risk for developing heart or brain vessel disease.
Juul and his team used data from The Copenhagen City Heart Study, a Danish study of 9,176 people that examined environmental and genetic risk factors for atherosclerosis. These healthy people were followed for 17 years to determine how many developed heart disease. In addition, 948 patients with atherosclerotic heart disease and 571 patients with atherosclerotic brain vessel disease were studied. A total of 10,695 were tested for the Arg213Gly genetic defect.
Ten percent of people not carrying the mutation, compared to 15 percent of individuals with the mutation, developed heart disease during the 17 years follow-up period. This translates into a 50 percent increase in the risk of heart disease. Likewise, carriers had 1.8 times the risk of non-carriers for brain vessel disease. This translates into an 80 percent increase or almost double the risk.
Free radicals are made in the body, but they can also come from cigarette smoke, alcohol intake, particulate air pollution, UV-rays from sunlight and some medicines.
Foods containing antioxidants, such as vitamin C and A, are thought to help fight heart disease and other chronic ailments, says Juul.
Researchers don’t know if adding antioxidants to the diet would help individuals with the Arg213Gly mutation and suggest more study is needed.
Co-authors are: Anne Tybjaerg-Hansen, M.D., D.M.Sc.; Rolf Steffensen, M.D; Henrik Sillesen, M.D. D.M.Sc.; Gorm Jensen, M.D., D.M.Sc.; Borge Nordestgaard, M.D., D.M.Sc.
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