A mutation in a gene for blood clotting dramatically increases the risk of heart disease in black but not white Americans, according to results from an ongoing study of more than 15,000 people.

“To my knowledge this is the first study of coronary heart disease to distinguish between ethnic groups,” says team leader Kenneth K. Wu of the University of Texas in Houston. The normal form of the gene encodes the protein thrombo-modulin, which dots the walls of blood vessels. This protein changes the blood- clotting enzyme thrombin into a form that actually prevents unwelcome clotting. A mutation of the gene derails this function by substituting a single amino acid in thrombomodulin’s structure. Earlier work found a correlation between heart attacks and this mutation but didn’t establish that the mutation causes heart attacks.

African Americans with the mutation were six times as likely to have heart disease than those without it, report Wu and his colleagues in Texas and at the University of Minnesota in Mirineapolis in the April 24 CIRCULATION. The mutation didn’t correspond to an increased risk of heart disease in white Americans.

Although the new data can’t explain this disparity between ethnic groups, the authors suggest that African Americans with low levels of normal thrombomodulin might be more sensitive to molecules that cause inflammation and hobble thrombomodulin. Or the mutated gene might simply accompany an unknown mutation that’s actually responsible for the increased risk. The researchers say their results should be interpreted with caution because the number of African Americans in the study with both heart disease and the mutation was small. Even so, Wu stresses, the results compel researchers to consider ethnic differences as the search for genes that cause disease. —J.N



Vol. 159. June 2, 2001, (pg. 349)

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