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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

Claudia Bozzini
1   Department of Clinical and Experimental Medicine, University of Verona
,
Domenico Girelli
1   Department of Clinical and Experimental Medicine, University of Verona
,
Francesco Bernardi
2   Department of Biochemistry and Molecular Biology, University of Ferrara
,
Paolo Ferraresi
2   Department of Biochemistry and Molecular Biology, University of Ferrara
,
Oliviero Olivieri
1   Department of Clinical and Experimental Medicine, University of Verona
,
Mirko Pinotti
2   Department of Biochemistry and Molecular Biology, University of Ferrara
,
Nicola Martinelli
1   Department of Clinical and Experimental Medicine, University of Verona
,
Franco Manzato
3   Laboratory of Clinical Pathology, Hospital “Carlo Poma”, Mantova
,
Simonetta Friso
1   Department of Clinical and Experimental Medicine, University of Verona
,
Giuliano Villa
1   Department of Clinical and Experimental Medicine, University of Verona
,
Francesca Pizzolo
1   Department of Clinical and Experimental Medicine, University of Verona
,
Federico Beltrame
4   Institute of Cardiology, University of Verona, Italy
,
Roberto Corrocher
1   Department of Clinical and Experimental Medicine, University of Verona
› Author AffiliationsFinancial support. Supported by grants from the Veneto Region, MIUR, and the Cariverona Foundation, Verona, Italy.
Further Information

Publication History

Received 26 February 2004

Accepted after resubmission 04 June 2004

Publication Date:
30 November 2017 (online)

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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
 

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