Originally created 04/27/01

Gene linked to increased heart-disease risk in blacks

Researchers have linked a gene involved in blood clotting to a six-fold increase in risk for heart disease among African Americans, according to a new report.

"Our results show that a single amino acid change in the thrombomodulin gene is an independent risk factor for heart disease in blacks," said Dr. Kenneth Wu, director of the Hematology and Vascular Biology Research Center at the University of Texas-Houston and lead author of the study published Tuesday in Circulation: Journal of the American Heart Association.

The same minute shift in the gene structure was not associated with heart-disease risk in Caucasians.

Wu said the findings "provide a genetic basis for differential risk factors of heart attacks between African Americans and whites" and also present a potential new tool for assessing heart-disease risk among blacks.

Thrombomodulin, a protein found in the lining of blood vessel walls, converts the enzyme thrombin from a clotting agent into an anti-clotting agent. By changing the sequence of proteins in the gene that contains instructions for making the anti-clotting agent, there are reduced levels of normal thrombomodulin.

This makes for an increased tendency for blood-vessel damage and blood clots. The same shift in gene structure has already been associated with an increased risk for heart attack.

The risk was identified from a long-term study of more than 15,000 men and women aged 45-64 from four different communities around the United States. People in the Atherosclerosis Risk in Communities study were first evaluated between 1987 and 1989 and have been re-examined every three years since. Testing included blood-pressure measurements and sampling of blood and DNA.

Researchers identified 467 individuals who developed heart disease. The sequence of proteins in the thrombomodulin gene was determined in 376 of those with heart disease, as well as in a sample of 461 participants who did not develop heart disease.

Each person carries two copies of the thrombomodulin gene, one from each parent. So a person can carry two unaltered forms of the gene, a regular form and an altered form, or two altered forms.

The study showed that blacks with at least one copy of the altered form had a 6.1 times greater risk for heart disease after other risk factors were taken into account.

But carrying an altered form did not significantly increase the heart-disease risk for whites. Having the two unaltered genes was more common in those without heart disease - present in 98 out of 105 healthy blacks and 237 out of 356 healthy whites.

Wu said it's not clear why the altered structure makes for a higher risk among blacks but not whites. However, he said the clotting gene may behave differently in different racial groups and that other genes that influence clotting may also influence heart-attack and stroke risk.

He also cautioned that it's too early to say that the altered gene can definitely be considered a marker for heart disease in all black Americans.

"It is likely that this structure is a risk factor for all blacks in the U.S., since this is a population-based study. However, I would like to caution that the number of African Americans with heart disease in the study group is relatively small."

Wu and his colleagues are now analyzing a larger number of heart-disease cases to try to substantiate the results of the study. They also want to study the risks for heart attack and stroke related to other clotting genes in both blacks and whites.

On the Net: http://www.americanheart.org


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