Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease.
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.


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.
Wu
K K
KK
Vascular Biology Research Center and Division of Hematology, Department of Internal Medicine, The University of Texas-Houston Health Science Center, Houston, TX 77030, USA.
Aleksic
N
N
Ahn
C
C
Boerwinkle
E
E
Folsom
A R
AR
Juneja
H
H
D000328:Adult; D044383:Black People; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D018180:Thrombomodulin / Q000235:genetics*
D018180:Thrombomodulin