Factor XIII Val34Leu polymorphism: Frequency in familial thrombophilia patients and the lack of its effect on plasma FXIII level and activity

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Abstract

Genetic susceptibility for familial thrombophilia includes several abnormalities in genes involved in the coagulation cascade. A recently discovered polymorphism in the factor XIII (FXIII) gene results in a valine to leucine change just three amino acids away from the thrombin activation/cleavage site (FXIII Val34Leu) and has been shown to be associated with decreased risk for arterial and venous thrombosis. Most recently, several reports suggested that the 34Leu allele results in higher plasma FXIII-A activity. The aim of this study was to investigate the association between FXIII Val34Leu and familial thrombophilia and to determine the FXIII-A antigen and activity levels in normal individuals of different genotypes. For investigating FXIII Val34Leu polymorphism at the DNA level a mutagenic primer (modified in its 3' end) which introduces a restriction site for Cfol was constructed. The activity of plasma FXIII-A was measured by a modified UV photometric assay and for the determination of plasma FXIII mass concentration a one-step sandwich ELISA method was developed:1 Among 399 healthy volunteers 40.3% heterozygotes and 5.3% homozygotes were found (allele frequency: 25.4%) which is not significantly different from the values observed in the Caucasian populations investigated, so far. In thrombophilia patients (n = 273) 40.7% heterozygotes and 6.6% homozygotes were observed giving an allele frequency of 26.9%. Odds ratios for carriers versus wild-type individuals and for homozygotes versus heterozygotes plus wild-type individuals were 1.07 and 1.27; respectively. These data do not support the protective effect of FXIII Val34Leu polymorphism against venous thrombosis. A total of 141 normal individuals (61 males and 80 females) were analyzed for FXIII-A mass concentration and activity. Both antigen and activity levels show a perfect Gaussian distribution. Mass concentration in wild-type, heterozygous and homozygous individuals was 21.7, 21.3 and 20.6 mg/L while plasma FXIII activity was 159, 155 and 152 U/L, respectively. The specific activities calculated from these data, were identical for the three genotypes (7.3, 7.3 and 7.4 U/mg). As the rate of thrornbin activation in mutant FXIII-A was higher than in wild-type, the lower activity of wild-type FXIII observed in earlier reports seems to be due to incomplete proteolytic activation.

Original languageEnglish
Pages (from-to)80
Number of pages1
JournalFibrinolysis and Proteolysis
Volume14
Issue numberSUPPL. 1
Publication statusPublished - 2000

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Factor XIII
Thrombophilia
Homozygote
Heterozygote
Gene Frequency
Venous Thrombosis
Genotype
Antigens
Normal Distribution
Valine
Genetic Predisposition to Disease
Thrombin
Leucine
Genes

ASJC Scopus subject areas

  • Hematology

Cite this

@article{f09ca250b3b54f3082125d465966ed64,
title = "Factor XIII Val34Leu polymorphism: Frequency in familial thrombophilia patients and the lack of its effect on plasma FXIII level and activity",
abstract = "Genetic susceptibility for familial thrombophilia includes several abnormalities in genes involved in the coagulation cascade. A recently discovered polymorphism in the factor XIII (FXIII) gene results in a valine to leucine change just three amino acids away from the thrombin activation/cleavage site (FXIII Val34Leu) and has been shown to be associated with decreased risk for arterial and venous thrombosis. Most recently, several reports suggested that the 34Leu allele results in higher plasma FXIII-A activity. The aim of this study was to investigate the association between FXIII Val34Leu and familial thrombophilia and to determine the FXIII-A antigen and activity levels in normal individuals of different genotypes. For investigating FXIII Val34Leu polymorphism at the DNA level a mutagenic primer (modified in its 3' end) which introduces a restriction site for Cfol was constructed. The activity of plasma FXIII-A was measured by a modified UV photometric assay and for the determination of plasma FXIII mass concentration a one-step sandwich ELISA method was developed:1 Among 399 healthy volunteers 40.3{\%} heterozygotes and 5.3{\%} homozygotes were found (allele frequency: 25.4{\%}) which is not significantly different from the values observed in the Caucasian populations investigated, so far. In thrombophilia patients (n = 273) 40.7{\%} heterozygotes and 6.6{\%} homozygotes were observed giving an allele frequency of 26.9{\%}. Odds ratios for carriers versus wild-type individuals and for homozygotes versus heterozygotes plus wild-type individuals were 1.07 and 1.27; respectively. These data do not support the protective effect of FXIII Val34Leu polymorphism against venous thrombosis. A total of 141 normal individuals (61 males and 80 females) were analyzed for FXIII-A mass concentration and activity. Both antigen and activity levels show a perfect Gaussian distribution. Mass concentration in wild-type, heterozygous and homozygous individuals was 21.7, 21.3 and 20.6 mg/L while plasma FXIII activity was 159, 155 and 152 U/L, respectively. The specific activities calculated from these data, were identical for the three genotypes (7.3, 7.3 and 7.4 U/mg). As the rate of thrornbin activation in mutant FXIII-A was higher than in wild-type, the lower activity of wild-type FXIII observed in earlier reports seems to be due to incomplete proteolytic activation.",
author = "I. Balogh and E. Katona and L. K{\'a}rp{\'a}ti and C. Pfliegler and L. Muszbek",
year = "2000",
language = "English",
volume = "14",
pages = "80",
journal = "Fibrinolysis and Proteolysis",
issn = "0268-9499",
publisher = "Churchill Livingstone",
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TY - JOUR

T1 - Factor XIII Val34Leu polymorphism

T2 - Frequency in familial thrombophilia patients and the lack of its effect on plasma FXIII level and activity

AU - Balogh, I.

AU - Katona, E.

AU - Kárpáti, L.

AU - Pfliegler, C.

AU - Muszbek, L.

PY - 2000

Y1 - 2000

N2 - Genetic susceptibility for familial thrombophilia includes several abnormalities in genes involved in the coagulation cascade. A recently discovered polymorphism in the factor XIII (FXIII) gene results in a valine to leucine change just three amino acids away from the thrombin activation/cleavage site (FXIII Val34Leu) and has been shown to be associated with decreased risk for arterial and venous thrombosis. Most recently, several reports suggested that the 34Leu allele results in higher plasma FXIII-A activity. The aim of this study was to investigate the association between FXIII Val34Leu and familial thrombophilia and to determine the FXIII-A antigen and activity levels in normal individuals of different genotypes. For investigating FXIII Val34Leu polymorphism at the DNA level a mutagenic primer (modified in its 3' end) which introduces a restriction site for Cfol was constructed. The activity of plasma FXIII-A was measured by a modified UV photometric assay and for the determination of plasma FXIII mass concentration a one-step sandwich ELISA method was developed:1 Among 399 healthy volunteers 40.3% heterozygotes and 5.3% homozygotes were found (allele frequency: 25.4%) which is not significantly different from the values observed in the Caucasian populations investigated, so far. In thrombophilia patients (n = 273) 40.7% heterozygotes and 6.6% homozygotes were observed giving an allele frequency of 26.9%. Odds ratios for carriers versus wild-type individuals and for homozygotes versus heterozygotes plus wild-type individuals were 1.07 and 1.27; respectively. These data do not support the protective effect of FXIII Val34Leu polymorphism against venous thrombosis. A total of 141 normal individuals (61 males and 80 females) were analyzed for FXIII-A mass concentration and activity. Both antigen and activity levels show a perfect Gaussian distribution. Mass concentration in wild-type, heterozygous and homozygous individuals was 21.7, 21.3 and 20.6 mg/L while plasma FXIII activity was 159, 155 and 152 U/L, respectively. The specific activities calculated from these data, were identical for the three genotypes (7.3, 7.3 and 7.4 U/mg). As the rate of thrornbin activation in mutant FXIII-A was higher than in wild-type, the lower activity of wild-type FXIII observed in earlier reports seems to be due to incomplete proteolytic activation.

AB - Genetic susceptibility for familial thrombophilia includes several abnormalities in genes involved in the coagulation cascade. A recently discovered polymorphism in the factor XIII (FXIII) gene results in a valine to leucine change just three amino acids away from the thrombin activation/cleavage site (FXIII Val34Leu) and has been shown to be associated with decreased risk for arterial and venous thrombosis. Most recently, several reports suggested that the 34Leu allele results in higher plasma FXIII-A activity. The aim of this study was to investigate the association between FXIII Val34Leu and familial thrombophilia and to determine the FXIII-A antigen and activity levels in normal individuals of different genotypes. For investigating FXIII Val34Leu polymorphism at the DNA level a mutagenic primer (modified in its 3' end) which introduces a restriction site for Cfol was constructed. The activity of plasma FXIII-A was measured by a modified UV photometric assay and for the determination of plasma FXIII mass concentration a one-step sandwich ELISA method was developed:1 Among 399 healthy volunteers 40.3% heterozygotes and 5.3% homozygotes were found (allele frequency: 25.4%) which is not significantly different from the values observed in the Caucasian populations investigated, so far. In thrombophilia patients (n = 273) 40.7% heterozygotes and 6.6% homozygotes were observed giving an allele frequency of 26.9%. Odds ratios for carriers versus wild-type individuals and for homozygotes versus heterozygotes plus wild-type individuals were 1.07 and 1.27; respectively. These data do not support the protective effect of FXIII Val34Leu polymorphism against venous thrombosis. A total of 141 normal individuals (61 males and 80 females) were analyzed for FXIII-A mass concentration and activity. Both antigen and activity levels show a perfect Gaussian distribution. Mass concentration in wild-type, heterozygous and homozygous individuals was 21.7, 21.3 and 20.6 mg/L while plasma FXIII activity was 159, 155 and 152 U/L, respectively. The specific activities calculated from these data, were identical for the three genotypes (7.3, 7.3 and 7.4 U/mg). As the rate of thrornbin activation in mutant FXIII-A was higher than in wild-type, the lower activity of wild-type FXIII observed in earlier reports seems to be due to incomplete proteolytic activation.

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