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Published in: Journal of Translational Medicine 1/2012

Open Access 01-12-2012 | Research

Prothrombotic gene variants as risk factors of acute myocardial infarction in young women

Authors: Rossella Tomaiuolo, Chiara Bellia, Antonietta Caruso, Rosanna Di Fiore, Sandro Quaranta, Davide Noto, Angelo B Cefalù, Pierpaolo Di Micco, Federica Zarrilli, Giuseppe Castaldo, Maurizio R Averna, Marcello Ciaccio

Published in: Journal of Translational Medicine | Issue 1/2012

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Abstract

Background

Acute myocardial infarction (AMI) in young women represent an extreme phenotype associated with a higher mortality compared with similarly aged men. Prothrombotic gene variants could play a role as risk factors for AMI at young age.

Methods

We studied Factor V Leiden, FII G20210A, MTHFR C677T and beta-fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females) and in 698 AMI (245 females) patients. The data were compared to those obtained in 909 unrelated subjects (458 females) from the general population of the same geographical area (southern Italy).

Results

In young AMI females, the allelic frequency of either FV Leiden and of FII G20210A was significantly higher versus the general population (O.R.: 3.67 for FV Leiden and O.R.: 3.84 for FII G20210A; p<0.001). Among AMI patients we showed only in males that the allelic frequency of the MTHFR C677T variant was significantly higher as compared to the general population. Such difference was due to a significantly higher frequency in AMI males of the MTHFR C677T variant homozygous genotype (O.R. 3.05).

Discussion and conclusion

Our data confirm that young AMI in females is a peculiar phenotype with specific risk factors as the increased plasma procoagulant activity of FV and FII. On the contrary, the homozygous state for the 677T MTHFR variant may cause increased levels of homocysteine and/or an altered folate status and thus an increased risk for AMI, particularly in males. The knowledge of such risk factors (that may be easily identified by molecular analysis) may help to improve prevention strategies for acute coronary diseases in specific risk-group subjects.
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Literature
1.
go back to reference Choudhury L, Marsh JD: Myocardial infarction in young patients. Am J Med. 1999, 107: 254-261. 10.1016/S0002-9343(99)00218-1.CrossRefPubMed Choudhury L, Marsh JD: Myocardial infarction in young patients. Am J Med. 1999, 107: 254-261. 10.1016/S0002-9343(99)00218-1.CrossRefPubMed
2.
go back to reference Doughty M, Mehta R, Bruckman D, Das S, Karavite D, Tsai T, Eagle K: Acute myocardial infarction in the young-The University of Michigan experience. Am Heart J. 2002, 143: 56-62. 10.1067/mhj.2002.120300.CrossRefPubMed Doughty M, Mehta R, Bruckman D, Das S, Karavite D, Tsai T, Eagle K: Acute myocardial infarction in the young-The University of Michigan experience. Am Heart J. 2002, 143: 56-62. 10.1067/mhj.2002.120300.CrossRefPubMed
3.
go back to reference Fournier JA, Cabezón S, Cayuela A, Ballesteros SM, Cortacero JA, Díaz De La Llera LS: Long-term prognosis of patients having acute myocardial infarction when </=40 years of age. Am J Cardiol. 2004, 94: 989-992. 10.1016/j.amjcard.2004.06.051.CrossRefPubMed Fournier JA, Cabezón S, Cayuela A, Ballesteros SM, Cortacero JA, Díaz De La Llera LS: Long-term prognosis of patients having acute myocardial infarction when </=40 years of age. Am J Cardiol. 2004, 94: 989-992. 10.1016/j.amjcard.2004.06.051.CrossRefPubMed
4.
go back to reference Marenberg ME, Risch N, Berkman LF, Floderus B, De Faire U: Genetic susceptibility to death from coronary heart disease in a study of twuins. N Engl J Med. 1994, 330: 1041-1046. 10.1056/NEJM199404143301503.CrossRefPubMed Marenberg ME, Risch N, Berkman LF, Floderus B, De Faire U: Genetic susceptibility to death from coronary heart disease in a study of twuins. N Engl J Med. 1994, 330: 1041-1046. 10.1056/NEJM199404143301503.CrossRefPubMed
5.
6.
go back to reference Kyrle PA, Rosendaal FR, Eichinger S: Risk assessment for recurrent venous thrombosis. Lancet. 2010, 376: 2032-2039. 10.1016/S0140-6736(10)60962-2.CrossRefPubMed Kyrle PA, Rosendaal FR, Eichinger S: Risk assessment for recurrent venous thrombosis. Lancet. 2010, 376: 2032-2039. 10.1016/S0140-6736(10)60962-2.CrossRefPubMed
7.
go back to reference Di Micco P, Di Fiore R, Niglio A, Quaranta S, Angiolillo A, Cardillo G, Castaldo G: Different outcome of six homozygotes for prothrombin A20210A gene variant. J Transl Med. 2008, 15: 36-CrossRef Di Micco P, Di Fiore R, Niglio A, Quaranta S, Angiolillo A, Cardillo G, Castaldo G: Different outcome of six homozygotes for prothrombin A20210A gene variant. J Transl Med. 2008, 15: 36-CrossRef
8.
go back to reference Kathiresan S, Yang Q, Larson MG, Camargo AL, Tofler GH, Hirschhorn JN, Gabriel SB, O'Donnell CJ: Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk. Arterioscler Thromb Vasc Biol. 2006, 26: 1405-1412. 10.1161/01.ATV.0000222011.13026.25.CrossRefPubMed Kathiresan S, Yang Q, Larson MG, Camargo AL, Tofler GH, Hirschhorn JN, Gabriel SB, O'Donnell CJ: Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk. Arterioscler Thromb Vasc Biol. 2006, 26: 1405-1412. 10.1161/01.ATV.0000222011.13026.25.CrossRefPubMed
9.
go back to reference Zheng Y, Liu EHC, Higgins JPT, Keavney BD, Lowe GDO, Collins R, Danesh J: Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66155 cases and 91307 controls. Lancet. 2006, 367: 651-658. 10.1016/S0140-6736(06)68263-9.CrossRef Zheng Y, Liu EHC, Higgins JPT, Keavney BD, Lowe GDO, Collins R, Danesh J: Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66155 cases and 91307 controls. Lancet. 2006, 367: 651-658. 10.1016/S0140-6736(06)68263-9.CrossRef
10.
go back to reference Mannucci PM, Asselta R, Duga S, Guella I, Spreafico M, Lotta L, Merlini PA, Peyvandi F, Kathiresan S, Ardissino D: The association of factor V Leiden with myocardial infarction is replicated in 1880 patients with premature disease. J Thromb Haemost. 2010, 8: 2116-2121. 10.1111/j.1538-7836.2010.03982.x.CrossRefPubMed Mannucci PM, Asselta R, Duga S, Guella I, Spreafico M, Lotta L, Merlini PA, Peyvandi F, Kathiresan S, Ardissino D: The association of factor V Leiden with myocardial infarction is replicated in 1880 patients with premature disease. J Thromb Haemost. 2010, 8: 2116-2121. 10.1111/j.1538-7836.2010.03982.x.CrossRefPubMed
11.
go back to reference Atherosclerosis, Thrombosis and Vascular Biology Italian Study Group: No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age. Circulation. 2003, 107: 1117-1122. 10.1161/01.CIR.0000051465.94572.D0.CrossRef Atherosclerosis, Thrombosis and Vascular Biology Italian Study Group: No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age. Circulation. 2003, 107: 1117-1122. 10.1161/01.CIR.0000051465.94572.D0.CrossRef
13.
go back to reference Ioannidis JPA, Trikalinos TA, Nizani EE, Contopoulos-Ioannidis DG: Genetic associations in large versus small studies: an empirical assessment. Lancet. 2003, 361: 567-571. 10.1016/S0140-6736(03)12516-0.CrossRefPubMed Ioannidis JPA, Trikalinos TA, Nizani EE, Contopoulos-Ioannidis DG: Genetic associations in large versus small studies: an empirical assessment. Lancet. 2003, 361: 567-571. 10.1016/S0140-6736(03)12516-0.CrossRefPubMed
14.
go back to reference Thygesen K, Alpert JS, White HD: On behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal Definition of Myocardial Infarction. Circulation. 2007, 116: 2634-2653. 10.1161/CIRCULATIONAHA.107.187397.CrossRefPubMed Thygesen K, Alpert JS, White HD: On behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal Definition of Myocardial Infarction. Circulation. 2007, 116: 2634-2653. 10.1161/CIRCULATIONAHA.107.187397.CrossRefPubMed
15.
go back to reference Scudiero O, Nardone G, Omodei D, Tatangelo F, Vitale DF, Salvatore F, Castaldo G: A mannose-binding lectin defective haplotype is a risk factor for gastric cancer. Clin Chem. 2006, 52: 1625-1627. 10.1373/clinchem.2006.071696.CrossRefPubMed Scudiero O, Nardone G, Omodei D, Tatangelo F, Vitale DF, Salvatore F, Castaldo G: A mannose-binding lectin defective haplotype is a risk factor for gastric cancer. Clin Chem. 2006, 52: 1625-1627. 10.1373/clinchem.2006.071696.CrossRefPubMed
16.
go back to reference Tomaiuolo R, Ruocco A, Salapete C, Carru C, Baggio G, Franceschi C, Zinellu A, Vaupel J, Bellia C, Lo Sasso B, Ciaccio M, Castaldo G, Deiana L: Activity of mannose-binding lectin in centenarians. Aging Cell. 2012, 11: 394-400. 10.1111/j.1474-9726.2012.00793.x.CrossRefPubMedPubMedCentral Tomaiuolo R, Ruocco A, Salapete C, Carru C, Baggio G, Franceschi C, Zinellu A, Vaupel J, Bellia C, Lo Sasso B, Ciaccio M, Castaldo G, Deiana L: Activity of mannose-binding lectin in centenarians. Aging Cell. 2012, 11: 394-400. 10.1111/j.1474-9726.2012.00793.x.CrossRefPubMedPubMedCentral
17.
go back to reference Bellia C, Tomaiuolo R, Caruso A, Sasso BL, Zarrilli F, Carru C, Deiana M, Zinellu A, Pinna S, Castaldo G, Deiana L, Ciaccio M: Fetuin-A serum levels are not correlated to kidney function in long-lived subjects. Clin Biochem. 2012, 45: 637-640. 10.1016/j.clinbiochem.2012.02.024.CrossRefPubMed Bellia C, Tomaiuolo R, Caruso A, Sasso BL, Zarrilli F, Carru C, Deiana M, Zinellu A, Pinna S, Castaldo G, Deiana L, Ciaccio M: Fetuin-A serum levels are not correlated to kidney function in long-lived subjects. Clin Biochem. 2012, 45: 637-640. 10.1016/j.clinbiochem.2012.02.024.CrossRefPubMed
18.
go back to reference Boekholdt SM, Bijsterveld NR, Moons AHM, Levi M, Büller HR, Peters RJG: Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction. Circulation. 2001, 104: 3063-3068. 10.1161/hc5001.100793.CrossRefPubMed Boekholdt SM, Bijsterveld NR, Moons AHM, Levi M, Büller HR, Peters RJG: Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction. Circulation. 2001, 104: 3063-3068. 10.1161/hc5001.100793.CrossRefPubMed
19.
go back to reference Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, Maemura K, Shindo T, Minamino T, Ohno M, Yamaoki K, Ogasawara K, Aizawa T, Suzuki S, Yazaki Y: Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation. 1997, 95: 2032-2036. 10.1161/01.CIR.95.8.2032.CrossRefPubMed Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, Maemura K, Shindo T, Minamino T, Ohno M, Yamaoki K, Ogasawara K, Aizawa T, Suzuki S, Yazaki Y: Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation. 1997, 95: 2032-2036. 10.1161/01.CIR.95.8.2032.CrossRefPubMed
20.
go back to reference Meleady R, Ueland PM, Blom H, Whitehead AS, Refsum H, Daly LE, Vollset SE, Donohue C, Giesendorf B, Graham IM, Ulvik A, Zhang Y, Bjorke Monsen AL, EC Concerted Action Project: Homocysteine and Vascular Disease: Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project. Am J Clin Nutr. 2003, 77: 63-70.PubMed Meleady R, Ueland PM, Blom H, Whitehead AS, Refsum H, Daly LE, Vollset SE, Donohue C, Giesendorf B, Graham IM, Ulvik A, Zhang Y, Bjorke Monsen AL, EC Concerted Action Project: Homocysteine and Vascular Disease: Thermolabile methylenetetrahydrofolate reductase, homocysteine, and cardiovascular disease risk: the European Concerted Action Project. Am J Clin Nutr. 2003, 77: 63-70.PubMed
21.
go back to reference Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG, MTHFR Studies Collaboration Group: MTHFR 677C>T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA. 2002, 288: 2023-2031. 10.1001/jama.288.16.2023.CrossRefPubMed Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG, MTHFR Studies Collaboration Group: MTHFR 677C>T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA. 2002, 288: 2023-2031. 10.1001/jama.288.16.2023.CrossRefPubMed
Metadata
Title
Prothrombotic gene variants as risk factors of acute myocardial infarction in young women
Authors
Rossella Tomaiuolo
Chiara Bellia
Antonietta Caruso
Rosanna Di Fiore
Sandro Quaranta
Davide Noto
Angelo B Cefalù
Pierpaolo Di Micco
Federica Zarrilli
Giuseppe Castaldo
Maurizio R Averna
Marcello Ciaccio
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2012
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-10-235

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