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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

Elisabetta Castoldi
1   From the Department of Biochemistry and Molecular Biology, Ferrara University, Italy
,
Jan Rosing
2   From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Nethrlands
,
Domenico Girelli
3   From the Institute of Medical Pathology, Chair of Internal Medicine, Verona University, Italy
,
Lico Hoekema
2   From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Nethrlands
,
Barbara Lunghi
1   From the Department of Biochemistry and Molecular Biology, Ferrara University, Italy
,
Federico Mingozzi
1   From the Department of Biochemistry and Molecular Biology, Ferrara University, Italy
,
Paolo Ferraresi
1   From the Department of Biochemistry and Molecular Biology, Ferrara University, Italy
,
Simonetta Friso
3   From the Institute of Medical Pathology, Chair of Internal Medicine, Verona University, Italy
,
Roberto Corrocher
3   From the Institute of Medical Pathology, Chair of Internal Medicine, Verona University, Italy
,
Guido Tans
2   From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Nethrlands
,
Francesco Bernardi
1   From the Department of Biochemistry and Molecular Biology, Ferrara University, Italy
› Author Affiliations
Further Information

Publication History

Received 06 September 1999

Accepted after resubmission 17 November 1999

Publication Date:
14 December 2017 (online)

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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
 

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