TY - JOUR
T1 - Potential thrombophilic mutations/polymorphisms in patients with no flow-limiting stenosis after myocardial infarction
AU - French, John K.
AU - Van de Water, Neil S.
AU - Sutton, Timothy M.
AU - Lund, Mayanna
AU - Gao, Wan Zhen
AU - McDowell, Joanne
AU - Liu-Stratton, Yiwen
AU - Pohorence, Jeanette
AU - Szymanski, Diane
AU - Goldschmidt-Clermont, Pascal
AU - White, Harvey D.
AU - Browett, Peter J.
AU - Cooke, Glen
AU - Becker, Richard C.
N1 - Funding Information:
From the aDepartment of Molecular Medicine, University of Auckland, Auckland, bHaematology Department, Auckland Hospital, Auckland, cCardiology Department, Green Lane Hospital, Auckland, New Zealand, dHeart and Lung Institute, Ohio State University, Columbus, Ohio, and the eDivision of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC. Presented in part at the 74th American Heart Association Annual Scientific Sessions, November 2001, Anaheim, Calif. Guest Editor for this manuscript was Richard C. Becker, MD, University of Massachusetts Medical Center, Worcester, Mass. Supported in part by grants from the Health Research Council of New Zealand and the Auckland Medical Research Foundation. Submitted February 19, 2002; accepted May 1, 2002. Reprint requests: John French, MB, PhD, FACC, Department of Cardiology, Green Lane Hospital, Private Bag 92189, Auckland 1030, New Zealand. E-mail: johnf@adhb.govt.nz Copyright 2003, Mosby, Inc. All rights reserved. 0002-8703/2003/$30.00 + 0 doi:10.1067/mhj.2003.29
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - 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.
AB - 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.
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U2 - 10.1067/mhj.2003.29
DO - 10.1067/mhj.2003.29
M3 - Article
C2 - 12514663
AN - SCOPUS:0037219632
VL - 145
SP - 118
EP - 124
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
IS - 1
ER -