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The Nijmegen Hemostasis Assay: Simultaneous Fluorogenic Measurement of Thrombin and Plasmin Generation in a Single Well

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Fibrinogen gene variation and ischemic stroke.

K Jood¹, J Danielson, C Ladenvall

¹Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.

Journal of Thrombosis and Haemostasis : JTH

|March 12, 2008

Summary

Genetic variations in fibrinogen gamma (FGG) and alpha (FGA) genes are linked to ischemic stroke risk. These FGG/FGA gene associations suggest qualitative changes in fibrinogen, not just levels, influence stroke.

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Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States

Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States

Published on: April 1, 2015

Area of Science:

Genetics
Cardiovascular Medicine
Biochemistry

Background:

Plasma fibrinogen level and fibrin clot structure are heritable traits implicated in ischemic stroke pathogenesis.
Understanding the genetic basis of fibrinogen is crucial for stroke risk assessment.

Purpose of the Study:

To investigate associations between variations in fibrinogen gamma (FGG), alpha (FGA), and beta (FGB) genes, plasma fibrinogen levels, and ischemic stroke.
To determine if genetic variations influence stroke risk independently of fibrinogen concentration.

Main Methods:

A case-control study involving 600 ischemic stroke cases and 600 matched population controls.
Plasma fibrinogen levels measured using an automated clot-rate assay.
Eight tagging single nucleotide polymorphisms (SNPs) selected to capture genetic variation in FGA, FGG, and FGB genes.

Main Results:

Plasma fibrinogen levels were independently associated with ischemic stroke across all subtypes.
Fibrinogen beta (FGB) gene variations (haplotypes) were associated with fibrinogen levels but not stroke.
Fibrinogen gamma (FGG) and alpha (FGA) gene variations (haplotypes) showed independent associations with ischemic stroke, irrespective of fibrinogen levels.

Conclusions:

Haplotypes within the FGG/FGA genes are associated with ischemic stroke risk.
This association appears to be mediated by qualitative alterations in fibrinogen structure rather than quantitative changes in plasma levels.
Genetic variations in FGG/FGA genes represent a novel pathway influencing ischemic stroke.