Fibrinogen gene variation and ischemic stroke.
BACKGROUND
Plasma fibrinogen level and fibrin clot structure are heritable traits that may be of importance in the pathogenesis of ischemic stroke.


OBJECTIVE
To investigate associations between variation in the fibrinogen gamma (FGG), alpha (FGA) and beta (FGB) genes, fibrinogen level, and ischemic stroke.


METHODS
The Sahlgrenska Academy Study on Ischemic Stroke comprises 600 cases and 600 matched population controls. Stroke subtypes were defined according to TOAST criteria. Plasma fibrinogen level was measured by an automated clot-rate assay. Eight tagging single nucleotide polymorphisms (SNPs) were selected to capture genetic variation in the FGA, FGG, and FGB genes.


RESULTS
Plasma fibrinogen was independently associated with overall ischemic stroke and all subtypes, both in the acute stage (P < 0.001) and at three-month follow-up (P < 0.05). SNPs belonged to two haplotype blocks, one containing the FGB gene and the other the FGG and FGA genes. FGB haplotypes were associated with fibrinogen level (P < 0.01), but not with ischemic stroke. In contrast, FGG/FGA haplotypes showed independent association to ischemic stroke but not to fibrinogen level. In an additive model with the most common FGG/FGA haplotype (A1) as reference, the adjusted odds ratios of ischemic stroke were 1.4 [95% confidence interval (95% CI) 1.1-1.8], P < 0.01, 1.4 (95% CI 1.0-1.8), P < 0.05, and 1.5 (95% CI 1.0-2.1), P < 0.05 for the A2, A3, and A4 FGG/FGA haplotypes, respectively.


CONCLUSIONS
FGG/FGA haplotypes show association to ischemic stroke. This association is independent of fibrinogen level, thus suggesting that the association between ischemic stroke and variation at the FGG/FGA genes is mediated by qualitative rather than quantitative effects on fibrin(ogen).
Jood
K
K
Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden.
Danielson
J
J
Ladenvall
C
C
Blomstrand
C
C
Jern
C
C
D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007511:Ischemia / Q000473:pathology*; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D005810:Multigene Family; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics*
D005340:Fibrinogen