The VITA Project: Heritability of Resistance to Activated Protein C

Alberto Tosetto; Giancarlo Castaman; Antonio Cappellari; Francesco Rodeghiero

doi:10.1055/s-0037-1614121

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 84(05): 811-814
DOI: 10.1055/s-0037-1614121

Review Article

Schattauer GmbH

The VITA Project: Heritability of Resistance to Activated Protein C

Alberto Tosetto

¹From the Hemophilia and Thrombosis Center, Department of Hematology, S. Bortolo Hospital, Vicenza, Italy

,

Giancarlo Castaman

¹From the Hemophilia and Thrombosis Center, Department of Hematology, S. Bortolo Hospital, Vicenza, Italy

,

Antonio Cappellari

¹From the Hemophilia and Thrombosis Center, Department of Hematology, S. Bortolo Hospital, Vicenza, Italy

,

Francesco Rodeghiero

¹From the Hemophilia and Thrombosis Center, Department of Hematology, S. Bortolo Hospital, Vicenza, Italy

› Author Affiliations

Abstract

Summary

Resistance to activated protein C (APC) is a risk factor for venous thromboembolism also in absence of the FV Leiden mutation. To evaluate the influence of genetic factors on APC resistance, we evaluated the heritability of the APC resistance phenotype in 1,519 sib-parent pairs randomly selected from the VITA Project. After adjustment for known influencing factors, a high heritability coefficient (0.58) was observed and parental response to APC was the single most important factor in predicting the corresponding phenotype in sibs. In 32 parentsib pairs in which phenotypic resistance to APC unrelated to FV Leiden was present in both parents and sibs, no additional mutation on the 306-aminoacid residue of FV (FV Cambridge and FV Hong Kong) was found. In these 32 parent-sib pairs, FVIII:C and vWf:Ag levels were not significantly increased and there was no excess prevalence of the R2 allele of exon 13 of FV gene. This study suggests that the response to APC is significantly influenced by genetic factors also at a population level, but the responsible mechanisms are still undefined.

Key words

APC resistance - genetic - Factor V - thrombophilia - epidemiology

Full Text

References

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