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Thromb Haemost 2000; 84(04): 595-600
DOI: 10.1055/s-0037-1614073
Review Article
Schattauer GmbH

Effect of Val34Leu Polymorphism on the Activation of the Coagulation Factor XIII-A

U. Wartiovaara
1   From the Department of Clinical Chemistry, University of Helsinki and the Laboratory Department of Helsinki University Central Hospital, Finland
,
H. Mikkola
2   Department of Molecular Medicine and Gene Therapy, Lund University, Sweden
,
G. Szôke
3   Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center of the University of Debredcen, Hungary
,
G. Haramura
3   Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center of the University of Debredcen, Hungary
,
L. Kárpáti
3   Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center of the University of Debredcen, Hungary
,
I. Balogh
3   Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center of the University of Debredcen, Hungary
,
R. Lassila
4   Wihuri Research Institute, Helsinki, Finland
,
L. Muszbek
3   Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center of the University of Debredcen, Hungary
,
A. Palotie
1   From the Department of Clinical Chemistry, University of Helsinki and the Laboratory Department of Helsinki University Central Hospital, Finland
5   Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA, USA
› Author AffiliationsThis study was supported by grants from the Juselius Foundation, the Clinical Research Institute of HUCH, the Finnish Association of Haematology, The Finnish Medical Foundation, the Helsinki University 350 Anniversary Foundation, The Ulla Hjelt Fund, the Hungarian National Research Fund (OTKA/030406), the Hungarian Ministry of Health (321/1996) and the Hungarian Academy of Sciences. The travel grant from European Thrombosis Research Organization to Ulla Wartiovaara for working at the University of Debredcen is gratefully acknowledged.
Further Information

Publication History

Received 06 July 1999

Accepted after resubmission 21 April 2000

Publication Date:
11 December 2017 (online)

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Summary

Coagulation factor XIII (FXIII) is a protransglutaminase involved in the last step of the coagulation cascade by stabilising the fibrin clot. Recently, a common variation (FXIII Val34Leu) has been associated with a decreased risk of myocardial infarction and deep venous thrombosis. Val34Leu is critically located near the thrombin activation site of FXIII-A. In this study we investigated its effects on the activation of FXIII. Both recombinant and platelet-derived FXIII Val34Leu variants were shown to be more susceptible to thrombin cleavage than the wild type FXIII. The rate of enzymatic activation of FXIII Val34Leu was found increased, however, the specific activity of fully activated wild type FXIII and the Val34Leu mutant did not differ. During the course of thrombin-induced activation of FXIII fibrin γ-chain dimerisation and α-chain polymerisation developed more rapidly with the Val34Leu mutant. The increased rate of fibrin stabilisation brought about by the Val34Leu FXIII seems to be paradoxically associated with a protective effect against pathological thrombosis.

Abbreviations: AP, activation peptide of factor XIII; FXIII, blood coagulation factor XIII; FXIII-A, factor XIII subunit A; FXIII-A’, proteolytically activated subunit A; FXIII-B, factor XIII subunit B; SDS PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis

Key words

Factor XIII - factor XIII Val34Leu - factor XIII activation - activation peptide - thrombin
 

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