Influence of polymorphisms in the factor VII gene promoter on activated factor VII levels and on the risk of myocardial infarction in advanced coronary atherosclerosis

Claudia Bozzini; Domenico Girelli; Francesco Bernardi; Paolo Ferraresi; Oliviero Olivieri; Mirko Pinotti; Nicola Martinelli; Franco Manzato; Simonetta Friso; Giuliano Villa; Francesca Pizzolo; Federico Beltrame; Roberto Corrocher

doi:10.1160/TH04-02-0130

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(03): 541-549
DOI: 10.1160/TH04-02-0130

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Influence of polymorphisms in the factor VII gene promoter on activated factor VII levels and on the risk of myocardial infarction in advanced coronary atherosclerosis

Authors

Claudia Bozzini

¹Department of Clinical and Experimental Medicine, University of Verona
Domenico Girelli

¹Department of Clinical and Experimental Medicine, University of Verona
Francesco Bernardi

²Department of Biochemistry and Molecular Biology, University of Ferrara
Paolo Ferraresi

²Department of Biochemistry and Molecular Biology, University of Ferrara
Oliviero Olivieri

¹Department of Clinical and Experimental Medicine, University of Verona
Mirko Pinotti

²Department of Biochemistry and Molecular Biology, University of Ferrara
Nicola Martinelli

¹Department of Clinical and Experimental Medicine, University of Verona
Franco Manzato

³Laboratory of Clinical Pathology, Hospital “Carlo Poma”, Mantova
Simonetta Friso

¹Department of Clinical and Experimental Medicine, University of Verona
Giuliano Villa

¹Department of Clinical and Experimental Medicine, University of Verona
Francesca Pizzolo

¹Department of Clinical and Experimental Medicine, University of Verona
Federico Beltrame

⁴Institute of Cardiology, University of Verona, Italy
Roberto Corrocher

¹Department of Clinical and Experimental Medicine, University of Verona

Abstract

Summary

In this study, we investigate the influence of three factor VII (FVII) gene polymorphisms on activated FVII levels (FVIIa), and also on the risk of myocardial infarction (MI) in patients with advanced coronary atherosclerotic disease (CAD). The –323A2 allele in the promoter is known to be associated with low FVII levels, and has been suggested to protect against MI in some studies. The –402GA promoter polymorphism, that in vitro has been associated with having opposite effect, is less well studied clinically. For this study, plasma FVIIa levels and three FVII gene polymorphisms were assessed in 934 subjects of both sexes, all with an angiographic documentation of coronary vessels. Our results show that two promoter polymorphisms, plasma cholesterol, and gender, were significant predictors of FVIIa levels. The –402A allele was associated to a significant increase of FVIIa levels in males (by 19.2%). In a selected clinical model including the patients with severe CAD, with or without a thrombotic complication (MI), male carriers of the –402A had an increased risk of MI (OR=1.79; 95% CI 1.15-2.80). The –323A2 allele was associated to a significant decrease in FVIIa (by 36.02% in males, and 39.7% in females). Male carriers of the –323A2 were protected from MI (OR=0.6; 95% CI 0.39-0.94), but only after correction for the confounding effect of combined heterozygosity for the promoter polymorphisms. We can conclude that FVII gene polymorphisms with an opposite effect on FVIIa levels may modulate the risk of MI in males with advanced CAD. This study highlights a “within-gene” interaction, and the need to explore polymorphisms in candidate gene(s) in detail.

Keywords

Factor VII - gene polymorphisms - myocardial infarction

Full Text

References

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