Epistatic and pleiotropic effects of polymorphisms in the fibrinogen and coagulation factor XIII genes on plasma fibrinogen concentration, fibrin gel structure and risk of myocardial infarction

2006 ◽  
Vol 95 (03) ◽  
pp. 420-427 ◽  
Author(s):  
Per Eriksson ◽  
Carl-Göran Ericsson ◽  
Anders Hamsten ◽  
Angela Silveira ◽  
Maria Mannila
Keyword(s):  
Myocardial Infarction ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Fibrin Clot ◽  
Pleiotropic Effects ◽  
Plasma Fibrinogen ◽  
Fibrinogen Concentration ◽  
Fibrin Gel ◽  
Coagulation Factor Xiii ◽  
Clot Structure

SummaryAn intricate interplay between the genes encoding fibrinogen gamma (FGG), alpha (FGA) and beta (FGB), coagulation factor XIII (F13A1) and interleukin6 (IL6) and environmental factors is likely to influence plasma fibrinogen concentration, fibrin clot structure and risk of myocardial infarction (MI). In the present study, the potential contribution of SNPs harboured in the fibrinogen, IL6 and F13A1 genes to these biochemical and clinical phenotypes was examined. A database and biobank based on 387 survivors ofa first MI and population-based controls were used. Sixty controls were selected according to FGG 9340T>C [rs1049636] genotype for studies on fibrin clot structure using the liquid permeation method. The multifactor dimensionality reduction method was used for interaction analyses. We here report that the FGA 2224G>A [rs2070011] SNP (9.2%), plasma fibrinogen concentration (13.1%) and age (8.1%) appeared as independent determinants of fibrin gel porosity. The FGA 2224G>A SNP modulated the relation between plasma fibrinogen concentration and fibrin clot porosity. The FGG-FGA*4 haplotype, composed of the minor FGG 9340C and FGA 2224A alleles, had similar effects, supporting its reported protective role in relation to MI. Significant epistasis on plasma fibrinogen concentration was detected between the FGA 2224G>A and F13A1 Val34Leu [rs5985] SNPs (p<0.001).The FGG 9340T>C and FGB 1038G>A [rs1800791] SNPs appeared to interact on MI risk, explaining the association of FGG-FGB haplotypes with MI in the absence of effects of individual SNPs. Thus, epistatic and pleiotropic effects of polymorphisms contribute to the variation in plasma fibrinogen concentration, fibrin clot structure and risk of MI.

scholarly journals The effect of blood coagulation factor XIII on fibrin clot structure and fibrinolysis

2014 ◽  
Vol 12 (2) ◽  
pp. 197-205 ◽  
Author(s):  
E. L. Hethershaw ◽  
A. L. Cilia La Corte ◽  
C. Duval ◽  
M. Ali ◽  
P. J. Grant ◽  
...  
Keyword(s):  
Blood Coagulation ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Fibrin Clot ◽  
Coagulation Factor Xiii ◽  
Clot Structure

scholarly journals Coagulation factor XIII activity predicts left ventricular remodelling after acute myocardial infarction

2020 ◽  
Vol 7 (5) ◽  
pp. 2354-2364 ◽  
Author(s):  
Anna Frey ◽  
Tobias Gassenmaier ◽  
Ulrich Hofmann ◽  
Dominik Schmitt ◽  
Georg Fette ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Left Ventricular ◽  
Ventricular Remodelling ◽  
Left Ventricular Remodelling ◽  
Coagulation Factor Xiii

scholarly journals Substitution of coagulation factor XIII partially restores scar healing after myocardial infarction in factor XIII knockout mice

2003 ◽  
Vol 41 (6) ◽  
pp. 395
Author(s):  
Matthias Nahrendorf ◽  
Kai Hu ◽  
Karl-Heinz Hiller ◽  
Christiane Waller ◽  
Stefan Gattenlöhner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Knockout Mice ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Coagulation Factor Xiii ◽  
Scar Healing

Coagulation factor XIII polymorphisms and the risk of myocardial infarction and ischaemic stroke in young women

2002 ◽  
Vol 116 (2) ◽  
pp. 376-382 ◽  
Author(s):  
Alexander P. Reiner ◽  
Michele B. Frank ◽  
Stephen M. Schwartz ◽  
Michael L. Linenberger ◽  
W. T. Longstreth ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischaemic Stroke ◽  
Young Women ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Coagulation Factor Xiii ◽  
Stroke In Young

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

2000 ◽  
Vol 84 (10) ◽  
pp. 595-600 ◽  
Author(s):  
H. Mikkola ◽  
G. Szôke ◽  
G. Haramura ◽  
L. Kárpáti ◽  
I. Balogh ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Specific Activity ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Coagulation Factor ◽  
Fibrin Clot ◽  
Coagulation Cascade ◽  
Wild Type ◽  
Subunit A ◽  
Coagulation Factor Xiii

SummaryCoagulation 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

Reduction of Coagulation Factor XIII Concentration in Patients with Myocardial Infarction, Cerebral infarction, and other Thromboembolic Disorders

1977 ◽  
Vol 38 (04) ◽  
pp. 0863-0873 ◽  
Author(s):  
Norma Alkjaersig ◽  
Anthony P. Fletcher ◽  
Martin Lewis ◽  
Roy Ittyerah
Keyword(s):  
Myocardial Infarction ◽  
Molecular Weight ◽  
Cerebral Infarction ◽  
Factor Xiii ◽  
Coagulation Factor ◽  
Inverse Correlation ◽  
Neurological Deficits ◽  
Intravascular Coagulation ◽  
Coagulation Factor Xiii ◽  
Patient Groups

SummaryCoagulation factor XIII and plasma fibrinogen chromatographic assays have been performed serially in patients suffering from acute myocardial and cerebral infarction, and in others with disseminated intravascular coagulation. The findings were compared with 2 groups of “controls”; normal clinically-well subjects and hospitalized patients with cerebral infarction who exhibited minimal, stable, or improving neurological deficits. Substantial depression of factor XIII concentrations developed in the 3 patient groups, together with concomitant significant increases in the proportion and concentration of plasma high molecular weight fibrin(ogen) complexes (HMWFC). An inverse correlation (p<0.05) between coagulation factor XIII concentration and percentage of HMWFC was demonstrated in the early stages of the illness. These findings suggest that depression of coagulation factor XIII concentration in these states, is secondary to extra vascular or intravascular coagulation and may reflect its degree.

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