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Gene Variant Protects against Heart Attack and Stroke

By Nancy Touchette

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Heart Disease

People who have a common variation in a gene that affects inflammation in the body may be protected against heart attack and stroke, a new study reports.

The study, published in the Journal of the American Medical Association, found that people with the variant produce lower levels of a protein called COX-2 than people with the normal form of the gene.

Francesco Cipollone and his colleagues at the G. d’Annunzio University of Chieti in Italy , examined two groups of 864 patients hospitalized over an 18-month period. The patients in one group were treated for heart attack or stroke, while the patients in the other group were treated for other conditions.

Patients with two copies of the protective gene variant had a 67 percent lower risk of heart attack and stroke compared to patients with two copies of the normal form of the gene. Patients with one normal and one variant gene had a 52 percent lower risk.

“It’s important to identify people who have a genetic risk for heart attack or stroke,” says Cipollone. “For example, if someone has mild hypertension, there is a tendency to treat it less aggressively. But their genetic profile might suggest a more aggressive treatment.”

Heart attack and stroke are thought to occur when atherosclerotic plaques rupture, and clog up blood vessels. The rupture of the plaque deposits is triggered in part by COX-2, or cyclooxygenase 2, which activates enzymes that chew up the plaque.

Many anti-inflammatory drugs such as aspirin and ibuprofen work by blocking COX-2 or a similar protein called COX-1. However, blocking COX-1 causes side effects such as gastrointestinal discomfort and bleeding.

In recent years, a new class of anti-inflammatory drugs has been developed that blocks COX-2 without affecting COX-1. But these drugs, such as Vioxx and Celebrex, do not work for everyone and have been linked to heart attacks and strokes in some patients.

“The new study is significant because it could help us begin to sort out why these drugs can affect people so differently,” says Stephen Prescott of The University of Utah, who first discovered the COX-2 variant.

Further research is needed to learn whether the COX-2 variant has protective effects in larger populations. If the new findings are confirmed, then knowing whether a person carries the variant could help doctors assess the patient’s risk for heart disease or stroke.

A test for the COX-2 variant is currently available in Italy and may appear in the United States later this year, according to Cipollone.

Cipollone, F. et al. A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke. JAMA 291, 2221-2228 (May 12, 2004).

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