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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
1   From the Hemophilia and Thrombosis Center, Department of Hematology, S. Bortolo Hospital, Vicenza, Italy
,
Giancarlo Castaman
1   From the Hemophilia and Thrombosis Center, Department of Hematology, S. Bortolo Hospital, Vicenza, Italy
,
Antonio Cappellari
1   From the Hemophilia and Thrombosis Center, Department of Hematology, S. Bortolo Hospital, Vicenza, Italy
,
Francesco Rodeghiero
1   From the Hemophilia and Thrombosis Center, Department of Hematology, S. Bortolo Hospital, Vicenza, Italy
› Author AffiliationsWe thank M. Simioni, A. Contri and C. Dall’Oste for the laboratory and molecular biology investigations. This study was supported by grants of the Veneto Region, Ricerca Sanitaria Finalizzata “Trombofilia Multigenica” and Fondazione Cassa di Risparmio di Verona, Vicenza, Belluno ed Ancona, Italy.
Further Information

Publication History

Received 12 January 2000

Accepted after resubmission 14 June 2000

Publication Date:
13 December 2017 (online)

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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
 

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