SearchPublisher and Institutes
You are here: Home :: Area NEM :: Medical science :: Human medicine
Ghassan J. Maghzal, Stephen O. Brennan, Peter M. George
Fibrinogen Bpolymorphisms do not directly contribute to an altered in vitro clot structure in humans
Fibrinogen B polymorphisms, such as the 455 G/A and the Arg448Lys amino acid substitution, have been shown to increase the risk of atherothrombotic disease. Although these polymorphisms are related to fibrinogen concentrations, their effect on fibrin clot structure has not been extensively studied. We examined the frequency of the fibrinogen B 455 G/A polymorphism in a group of myocardial infarction (MI) patients. There was no association between this polymorphism and MI. However, we found that patients homozygous for the rare 455 A allele had a higher average age at first MI. A similar result was found for individuals homozygous for the B 448 Lys allele who also had a higher age at first MI. We subsequently studied the clotting properties of purified Arg448 and Lys448 fibrinogens in vitro and found that these fibrinogens did not significantly differ in their polymerisation, fibrinolysis kinetics or in their clot permeation properties. Mass spectrometry analysis of endoproteinase Asp-N digests of B chains revealed that the Lys448 and the Arg448 chains were expressed in approximately equal proportions in a heterozygote Arg448Lys individual. Our results demonstrate that the fibrinogen B 455 G/A polymorphism is not associated with myocardial infarction and further-more the closely linked B Arg448Lys protein coding variation does not have an influence on the function nor the structure of the protein in a purified system.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 90, 12/2003
Pages: 1021 - 1028