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Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease.

TitleThrombomodulin Ala455Val polymorphism and risk of coronary heart disease.
Publication TypeJournal Article
Year of Publication2001
AuthorsWu KK, Aleksic N, Ahn C, Boerwinkle E, Folsom AR, Juneja H
Corporate AuthorsAtherosclerosis Risk in Communities Study(ARIC) Investigators
JournalCirculation
Volume103
Issue10
Pagination1386-9
Date Published2001 Mar 13
ISSN1524-4539
KeywordsAdult, African Continental Ancestry Group, Cohort Studies, Coronary Disease, Female, Genetic Predisposition to Disease, Genetic Testing, Humans, Male, Middle Aged, Polymorphism, Genetic, Prospective Studies, Risk Factors, Thrombomodulin
Abstract

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.

DOI10.1161/01.cir.103.10.1386
Alternate JournalCirculation
PubMed ID11245641
Grant ListN01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States