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(Circulation. 2001;103:1386.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Thrombomodulin Ala455Val Polymorphism and Risk of Coronary Heart Disease

Kenneth K. Wu, MD, PhD; Nena Aleksic, PhD; Chul Ahn, PhD; Eric Boerwinkle, PhD; Aaron R. Folsom, MD; Harinder Juneja, MD; for the Atherosclerosis Risk in Communities Study (ARIC) Investigators

From the Vascular Biology Research Center and Division of Hematology, Department of Internal Medicine (K.K.W., N.A., H.J.), Division of General Medicine, Department of Internal Medicine (C.A.), and Department of Human Genetics (E.B.), The University of Texas-Houston Health Science Center, Houston, Tex; and Division of Epidemiology, The University of Minnesota, School of Public Health, Minneapolis, Minn (A.R.F.).

Background—Thrombomodulin (TM) is expressed on the endothelial surface and plays an important role in vasoprotection. A common polymorphism of TM at amino acid position 455 with an alanine (A) to valine (V) transition was previously reported to be associated cross-sectionally with acute myocardial infarction. Whether this single nucleotide polymorphism predicts risk of developing coronary heart disease (CHD) is unclear.

Methods and Results—Within a large cohort study, we identified 467 incident CHD cases during an average of 5 years of follow-up. We determined TM-455 genotypes on 376 CHD cases (23% black, 77% white) and a reference sample of 461. The AA genotype was significantly more prevalent in noncases than in cases (P=0.016). The prevalences of the AA genotype in noncase blacks and whites were 93% and 67%, respectively. The AA genotype frequency was significantly reduced in black cases versus noncases (P=0.018). It was also lower in white cases than in noncases, but the difference was not statistically significant (P=0.066). Weighted proportional hazards regression analysis after adjustment for age, sex, and other CHD risk factors showed that having the V allele increased risk of CHD by 6.1-fold (risk ratio 6.1, 95% CI 1.7 to 22.9) in blacks but did not significantly increase the risk in whites.

Conclusions—The TM A455V polymorphism predicts risk of developing CHD in blacks.

Key Words: thrombomodulin • genetics • coronary disease

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