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DOI: 10.1055/s-0037-1614552
Factor XIII Val34Leu Is a Genetic Factor Involved in the Aetiology of Venous Thrombosis
Publication History
Received
29 October 1998
Accepted after resubmission
22 January 1999
Publication Date:
09 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199905/lookinside/thumbnails/10.1055s-0037-1614552-1.jpg)
Summary
A mutation in the factor XIII gene (FXIII Val34Leu) gene was recently reported to confer protection against myocardial infarction, but its relationship with venous thrombosis is unknown. In addition, a mutation in the 5’-untranslated region of the FXII gene (46 C→T) was identified which is associated with low plasma levels of the protein. Its prevalence in patients with venous thrombosis is also unknown. We investigated the frequency of the FXIII Val34Leu and FXII 46 C→T mutations in 189 patients with deep venous thrombosis and in 187 age-, gender- and race-matched controls. FXIII Val34Leu was detected in 38.6% of the patients and in 41.2% of the controls. Interestingly, homozygosity for the FXIII mutation was found in 1.6% of the patients and in 9.6% of the controls, yielding an odds ratio (OR) for venous thrombosis of 0.16 (95% CI: 0.05-0.5). The OR for hetero-zygotes was 1.1 (95% CI: 0.7-1.7). The FXII 46 C→T mutation was detected in 46.0% of the patients and in 48.6% of the controls. The OR for heterozygotes was 0.9 (95% CI: 0.6-1.4) and for homozygotes the OR was 0.8 (95% CI: 0.3-1.9). Our data indicate that the FXII 46 C→T mutation is unlikely to be a major risk factor for venous thrombotic disease. In contrast, the homozygous state for FXIII Val34Leu is a strong protective factor against venous thrombosis, which emerges as a novel genetic factor involved in the aetiology of thrombophilia.
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References
- 1 De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: pathogenesis, clinical syndromes, and management.. Blood 1996; 87: 3531-44.
- 2 Seligsohn U, Zivelin A. Thrombophilia as a multigenic disorder.. Thromb Haemost 1997; 78: 297-301.
- 3 Dählback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognised mechanism characterised by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C.. PNASUSA 1993; 90: 1004-8.
- 4 Bertina R, Koeleman B, Koster T, Rosendaal F, Dirven R, De Ronde H, van der Velden P, Reitsma P. Mutation in blood coagulation factor V associated with resistance to activated protein C.. Nature 1994; 369: 64-7.
- 5 Poort SW, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis.. Blood 1996; 88: 3698-703.
- 6 Mikkola H, Syrjälä M, Rasi V, Vahtera E, Hämäläinen E, Peltonen L, Palotie A. Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels.. Blood 1994; 84: 517-25.
- 7 Kohler HP, Stickland MH, Ossei-Gerning N, Carter A, Mikkola H, Grant PJ. Association of a common polymorphism in the factor XIII gene with myocardial infarction.. Thromb Haemost 1998; 79: 8-13.
- 8 Catto AJ, Kohler HP, Bannan S, Stickland M, Carter A, Grant PJ. Factor XIII Val34Leu. A novel association with primary intracerebral hemorrhage.. Stroke 1998; 29: 813-6.
- 9 Kangsadalampai S, Board PG. The Val34Leu polymorphism in the A subunit of coagulation factor XIII contributes to the large normal range in activity and demonstrates that the activation peptide plays a role in catalytic activity.. Blood 1998; 92: 2766-70.
- 10 Kohler HP, Ariëns RAS, Whitaker P, Grant PJ. A common coding polymorphism in the FXIII A-subunit gene (FXIII VAL34LEU) affects cross-linking activity.. Thromb Haemost 1998; 80: 704
- 11 Winter M, Gallimore M, Jones DW. Should factor XII assays be included in thrombophilia screening?. Lancet 1995; 346: 52
- 12 Pandita D, Steen P, Potti A. Risk factors for deep venous thrombosis of the upper extremities.. Ann Int Med 1997; 127: 1129
- 13 Koster T, Rosendaal FR, Briët E, Vandenbroucke JP. John Hageman’s factor and deep-vein thrombosis: Leiden Thrombophilia Study.. Br J Haematol 1994; 87: 422-4.
- 14 Kanaji T, Okamura T, Osaki K, Kuroiwa M, Shimoda K, Hamasaki N, Niho Y. A common genetic polymorphism (46 C to T substitution) in the 5’-untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level.. Blood 1998; 91: 2010-4.
- 15 Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJH, den Heijer M, Kluijtmans LAJ, van den Heuvel LP, Rozen R. A candidate risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.. Nat Genet 1995; 10: 111-3.
- 16 Woolf B. On estimating the relation between blood group and disease.. Am J Hum Genet 1955; 19: 251
- 17 Arruda VR, von Zuben PM, Chiaparini LC, Annichino-Bizzacchi JM, Costa FF. The mutation Ala677→Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis.. Thromb Haemost 1997; 77: 818-21.