The factor VIII D1241E polymorphism is associated with decreased factor VIII activity and not with activated protein C resistance levels

Daniela Scanavini; Cristina Legnani; Barbara Lunghi; Federico Mingozzi; Gualtiero Palareti; Francesco Bernardi

doi:10.1160/TH04-09-0629

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(03): 453-456
DOI: 10.1160/TH04-09-0629

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

The factor VIII D1241E polymorphism is associated with decreased factor VIII activity and not with activated protein C resistance levels

Authors

Daniela Scanavini

¹Department of Biochemistry and Molecular Biology, Ferrara University, Italy
Cristina Legnani

²Department of Angiology, Unità Ricerca Clinica sulla Trombofilia “Marino Golinelli“, University Hospital S. Orsola-Malpighi, Bologna, Italy
Barbara Lunghi

¹Department of Biochemistry and Molecular Biology, Ferrara University, Italy
Federico Mingozzi

¹Department of Biochemistry and Molecular Biology, Ferrara University, Italy

³Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania Medical Center, Philadelphia, USA
Gualtiero Palareti

²Department of Angiology, Unità Ricerca Clinica sulla Trombofilia “Marino Golinelli“, University Hospital S. Orsola-Malpighi, Bologna, Italy
Francesco Bernardi

¹Department of Biochemistry and Molecular Biology, Ferrara University, Italy

Abstract

Summary

Elevated factor VIII (FVIII) levels are a recognized risk factor for venous thrombosis. Recently, family studies suggested that the G allele of the 3951C/G (D1241E) FVIII polymorphism is associated to lower FVIII activity. We investigated in case-control studies both biological effects (FVIII levels and activated protein C sensitivity ratio) and clinical associations (venous thromboembolism) of the D1241E change. Among 145 healthy and 150 thrombotic women, not carriers of known thrombophilic defects, the 1241E allele was associated with 11% reduced (t-test, P< 0.05) FVIII levels. The effect on activated protein C sensitivity ratio was not statistically significant. Carriership of the 1241E allele, potentially conferring protection from thrombosis, was found in 22.8% of controls and in 15.3% of cases. In an additional cohort of factor V Leiden carriers (n=283), carriership of the 1241E allele was 25.2% among 143 asymptomatic subjects and 17.1% among 140 thrombotic patients. Our data do not indicate a specific interaction with factor V Leiden. These genotype distributions suggest a mild protective effect from venous thrombosis conferred by 1241E FVIII, masked by other genetic and/or environmental components, and detectable only in very large population studies. Our findings point toward the presence of genetic determinant of coagulation factor levels with a biologically significant role, but with a poor predictive value to estimate thrombotic risk beyond established risk factors.

Keywords

FVIII levels - FVIII polymorphisms - thrombosis - APC resistance

Full Text

References

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