Mutations in the R2 FV Gene Affect the Ratio between the Two FV Isoforms in Plasma

Elisabetta Castoldi; Jan Rosing; Domenico Girelli; Lico Hoekema; Barbara Lunghi; Federico Mingozzi; Paolo Ferraresi; Simonetta Friso; Roberto Corrocher; Guido Tans; Francesco Bernardi

doi:10.1055/s-0037-1613821

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 83(03): 362-365
DOI: 10.1055/s-0037-1613821

Rapid Communications

Schattauer GmbH

Mutations in the R2 FV Gene Affect the Ratio between the Two FV Isoforms in Plasma

Authors

Elisabetta Castoldi

¹From the Department of Biochemistry and Molecular Biology, Ferrara University, Italy
Jan Rosing

²From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Nethrlands
Domenico Girelli

³From the Institute of Medical Pathology, Chair of Internal Medicine, Verona University, Italy
Lico Hoekema

²From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Nethrlands
Barbara Lunghi

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

¹From the Department of Biochemistry and Molecular Biology, Ferrara University, Italy
Paolo Ferraresi

¹From the Department of Biochemistry and Molecular Biology, Ferrara University, Italy
Simonetta Friso

³From the Institute of Medical Pathology, Chair of Internal Medicine, Verona University, Italy
Roberto Corrocher

³From the Institute of Medical Pathology, Chair of Internal Medicine, Verona University, Italy
Guido Tans

²From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Nethrlands
Francesco Bernardi

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

Abstract

Summary

Molecular genetics and biochemical studies were performed in homozygotes for the R2 allele (4070G) in the factor V gene, most of them affected by coronary artery disease. Novel polymorphisms (G642T, 156Ser; T1328C, 385Met/Thr), among which a functional candidate (A6755G, 2194Asp/Gly) located in the C2 domain of FV, were identified in the R2 gene. In chromatographic studies R2 FV appeared qualitatively identical to normal FV. However, a relative increase of the more thrombogenic and more glycosylated FV isoform (FV1) was observed in plasma of 2194Gly homozygotes (mean FV1/FV2 ratio 0.71, 95% CI 0.66-0.77) as compared to R2-free controls (0.37, 95% CI 0.34-0.40). We conclude that carriership of the R2 FV gene is associated with an imbalance between the two functionally different FV isoforms, and propose that genetically determined differential glycosylation of FV could represent a novel mechanism of thrombotic disease.

Keywords

R2 allele - functional polymorphism - FV isoform - FV assay - CAD

Full Text

References

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