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Study shows thrombomodulin variation associated with increased risk for heart disease in African Americans
By Sharon Guynup

Researchers have found that a single nucleotide polymorphism (SNP) of the thrombomodulin gene is an independent risk factor for coronary heart disease (CHD) among African Americans.

Thrombomodulin (TM) is a glycoprotein that is expressed on the surface of endothelial cells. It protects blood vessels and reduces blood clots. Kenneth Wu, of the University of Texas-Houston Health Science Center, and his colleagues suspected that reduced levels of TM might make the heart more susceptible to vascular damage and thrombosis. Their research intention was to identify the frequency of a previously reported alanine-to-valine polymorphism located at amino acid position 455 (A455V) and to determine if this change was statistically linked to a greater incidence of heart disease.

Genomic DNA from 376 heart patients was compared with that of 461 healthy individuals. The researchers discovered among the entire study cohort that carrying one or two copies of the valine thrombomodulin variant was associated with a 60 percent increased risk of coronary heart disease compared with individuals who carry two copies of the alanine variant.

Statistical adjustments for age, race, sex, and a range of other CHD risk factors revealed that African Americans carrying one or two copies of the valine polymorphism had a 6-fold increased risk of heart disease. But surprisingly, the genotype was not associated with any risk among whites.

The influence of the TM-455 mutation remains a mystery: It could serve as a marker for a neighboring polymorphism, it may induce a greater compromise of TM activity in African Americans, or CHD risk factors may differ among races. Larger studies are still needed.

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Wu, K.K. et al. Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease. Circulation 103, 1386-1389 (March 13, 2001).

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