Potential thrombophilic mutations/polymorphisms in patients with no flow-limiting stenosis after myocardial infarction

John K. French, Neil S. Van de Water, Timothy M. Sutton, Mayanna Lund, Wan Zhen Gao, Joanne McDowell, Yiwen Liu-Stratton, Jeanette Pohorence, Diane Szymanski, Pascal Goldschmidt-Clermont, Harvey D. White, Peter J. Browett, Glen Cooke, Richard C. Becker

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Abstract

Background: Although inherited thrombophilias are more common in patients with venous thromboembolism, their influence on the development of myocardial infarction (MI) requires clarification. Methods and Results: To determine whether there are increased frequencies of mutations/polymorphisms in 14 genes potentially causing thrombophilia in patients with no flow-limiting stenoses after MI compared with patients with ≥1 flow-limiting stenosis of >50%, we studied 395 patients (60 with no flow-limiting stenosis) who underwent angiography at approximately 1 month. The mutations/polymorphisms studied included Factor V Leiden, prothrombin variant G20210A, β-fibrinogen 448 (G/A), endothelial protein C receptor (23-base pair insertion), methyl tetrahydrofolate reductase 677. (C/T), platelet glycoprotein IIIa PIA1/A2, plasminogen activator inhibitor-1 4G/5G, angiotensin II type 1 receptor (A/C), hemochromatosis gene 282 (G/A), nitric oxide synthase (NOS) (3 forms: eNOS, eNOS3, eNOS4), p22 phox of NADPH oxidase C242T, and angiotensin-converting enzyme insertion/deletion polymorphism. The frequencies of Factor V Leiden and the β-fibrinogen 448 A allele were higher in patients with no flow-limiting stenosis than in patients with ≥1 stenosis (11.7% vs 3.6%, odds ratio [OR] 3.6, 95% CI 1.3-9.4, P = .015; and 42% vs 27%, OR 2.0, 95% CI 1.1-3.5, P = .018, respectively), and there was a trend toward an increased frequency of prothrombin variant G20210A (6.7% vs 2.1%, OR 3.4, 95% CI 0.95-11.8, P = .069). However, in patients with no flow-limiting stenosis after MI the frequencies of the other gene mutations/polymorphisms were not increased. Also, there were no significant interactions between any of these 14 mutation/polymorphisms, major cardiovascular risk factors, and the absence of any flow-limiting stenosis, except for Factor V Leiden and hypertension (OR 6.34, 95% CI 2.67-100, P = .004). Conclusions: Patients with no flow-limiting stenosis after MI had increased frequencies of 2 inherited thrombophilias (Factor V Leiden and β-fibrinogen 448 A allele), and there was a trend toward an increased frequency of prothrombin variant G20210A compared with patients with ≥1 stenosis. These data suggest that polymorphisms/mutations in some gene products influencing coagulation may influence the pathogenesis of MI.

Original languageEnglish (US)
Pages (from-to)118-124
Number of pages7
JournalAmerican Heart Journal
Volume145
Issue number1
DOIs
StatePublished - Jan 1 2003

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

French, J. K., Van de Water, N. S., Sutton, T. M., Lund, M., Gao, W. Z., McDowell, J., Liu-Stratton, Y., Pohorence, J., Szymanski, D., Goldschmidt-Clermont, P., White, H. D., Browett, P. J., Cooke, G., & Becker, R. C. (2003). Potential thrombophilic mutations/polymorphisms in patients with no flow-limiting stenosis after myocardial infarction. American Heart Journal, 145(1), 118-124. https://doi.org/10.1067/mhj.2003.29