Association of a Common Polymorphism in the Factor XIII Gene With Venous Thrombosis

Catto, Andrew J.; Köhler, Hans Peter; Coore, Julie; Mansfield, Michael; Stickland, M. H.; Grant, Peter J.

doi:10.1182/blood.v93.3.906.403k24_906_908

Cited by 68 publications

(85 citation statements)

References 6 publications

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“…One of the variations in the FXIII A gene, the Val34Leu polymorphism, has been correlated with thrombosis in a case–control study of 221 patients. Patients with thrombosis had an increased prevalence of the Val/Val genotype and a lower prevalence of the Val/Leu phenotype 56 . The study also showed that homozygous individuals carry a significantly higher activity of the enzyme than individuals with the wildtype genotype and heterozygous carry an intermediate value.…”

Section: Factor XIIImentioning

confidence: 76%

Inherited Thrombophilia: Impact on Human Reproduction

Buchholz

Thaler

2003

American J Rep Immunol

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The development of thrombotic disorders is a major threat for young women during pregnancy. It is one of the main causes of pregnancy-related disorders, which may also result in harm for the conceptus. Successful pregnancies require an even balance of coagulation and fibrinolysis, in order to secure stabilization of the basal plate as well as adequate placental perfusion. Thrombophilia is a laboratory definition for pre-disposing factors of thrombosis, which can be inherited or acquired. Many individuals, who carry a thrombotic defect remain asymptomatic, at least until additional boosting factors arise. The documentation of thrombophilic causes of recurrent miscarriage or pregnancy-related disorders is important, because of availability of effective early treatment. There is a rapidly growing awareness on the relationship of genetic factors influencing hemostasis and pregnancy-related disorders. The aim of our review is to summarize this knowledge, focusing on common genetic variations.

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Section: Factor XIIImentioning

confidence: 76%

Inherited Thrombophilia: Impact on Human Reproduction

Buchholz

Thaler

2003

American J Rep Immunol

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“…The presence of Leu instead of Val within codon 34 (FXIIIVal34Leu) in the 2 nd exon of the FXIII A-subunit gene has been associated with high FXIII specific activity [Anwar et al 1999]. The FXIIIVal34Leu (G → T) mutation has been associated with myocardial and brain infarction Elbaz et al 2000;Rallidis et al 2008;Shafey et al 2007;Wartiovaara et al 1999], venous thrombosis, and familial thrombophilia [Catto et al 1999;Balogh et al 2000;Franco et al 2000;Vossen and Rosendaal 2005;Wells et al 2006]. It has been observed that severe FXIII deficiency is a rare homozygous disorder, but, heterozygous FXIII deficiency is more common [Ichinose and Davie 1988;.…”

Section: Resultsmentioning

confidence: 99%

The Val34Leu genetic variation in the A Subunit of Coagulation Factor XIII in recurrent spontaneous abortion

Bagheri

Rad

Omrani

et al. 2011

Systems Biology in Reproductive Medicine

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The present study was carried out to assess the frequencies of factor XIII (FXIII) Val34Leu genetic variation in the patients with recurrent spontaneous abortion and healthy fertile women of Azeri Turkish origin. A total of 54 patients with recurrent spontaneous abortion and 46 healthy fertile women as controls were studied for the FXIII Val34Leu genetic variation by a RFLP-PCR method. Statistical analysis showed that patients (χ 2 = 2.4, p value = 0.292) and controls (χ 2 = 1.035, p value = 0.596) were in agreement with Hardy-Weinberg equilibrium. The Leu allele frequency was 0.18 and 0.13 in patients and controls, respectively. FXIII Leu34Leu (homozygous for 34Leu) genotype was not found in patients and controls. FXIII Val/Leu and Val/Val genotype frequencies were 19 (35.19%) and 31 (64.81%) in patients and 12 (26.09%) and 34 (73.91%) in controls, respectively. FXIII 34Leu allele and Val34Leu genotypes were more common in the case group containing individuals with unexplained RSA but the differences of FXIII Val34Leu (G/T genotype) (odds ratio = 0.65 (0.25 < OR < 1.67) corresponding to 95% CI, χ 2 = 0.96, p value = 0.32) and FXIII 34Leu (T allele) (odds ratio = 0.70 (0.30 < OR < 1.64) corresponding to 95% CI, χ 2 = 0.78, p value = 0.37) was not statistically significant. These results suggest that factor XIII Val34Leu genetic variation is not associated with recurrent spontaneous abortion.

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“…To date, there have been 2 studies analyzing the possible association of FXIII Val34Leu polymorphism with venous thrombosis. Catto et al 15 demonstrated that the Leu34 allele represents a significant protection against venous thrombosis. Franco et al 16 reported that the protective effect was restricted to homozygotes.…”

Section: Discussionmentioning

confidence: 99%

“…Protection against venous thrombosis by the Leu34 allele has also been reported. 15,16 The biochemical consequences of FXIII-A Val34Leu polymorphism are unknown, and no scientifically sound hypothesis for the biochemical mechanism of such protective effect has been offered. In theory, a polymorphism may influence the plasma level of FXIII, the process of activation, and the specific transglutaminase activity of FXIIIa.…”

Section: And Muszbek Et Al 2 )mentioning

confidence: 99%

Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia

Balogh

Szőke

Kárpáti

et al. 2000

Blood

107

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Val34Leu polymorphism of the A subunit of coagulation factor XIII (FXIII-A) is located in the activation peptide (AP) just 3 amino acids away from the thrombin cleavage site. This mutation has been associated with a protective effect against occlusive arterial diseases and venous thrombosis; however, its biochemical consequences have not been explored. In the current study it was demonstrated that the intracellular stability and the plasma concentration of FXIII of different Val34Leu genotypes are identical, which suggests that there is no difference in the rate of synthesis and externalization of wild-type and mutant FXIII-A. In contrast, the release of AP by thrombin from the Leu34 allele proceeded significantly faster than from its wild-type Val34 counterpart. By molecular modeling larger interaction energy was calculated between the Leu34 variant and the respective domains of thrombin than between the Val34 variant and thrombin. In agreement with these findings, the activation of mutant plasma FXIII by thrombin was faster and required less thrombin than that of the wild-type variant. Full thrombin activation of purified plasma FXIII of different genotypes, however, resulted in identical specific transglutaminase activities. Similarly, the mean specific FXIII activity in the plasma was the same in the groups with wild-type, heterozygous, and homozygous variants. Faster activation of the Leu34 allele hardly could be associated with its presumed protective effect against venous thrombosis. No such protective effect was observed in a large group of patients with familial thrombophilia.

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Association of a Common Polymorphism in the Factor XIII Gene With Venous Thrombosis

Cited by 68 publications

References 6 publications

Inherited Thrombophilia: Impact on Human Reproduction

Inherited Thrombophilia: Impact on Human Reproduction

The Val34Leu genetic variation in the A Subunit of Coagulation Factor XIII in recurrent spontaneous abortion

Val34Leu polymorphism of plasma factor XIII: biochemistry and epidemiology in familial thrombophilia

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