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Fibrinogen gene variation and ischemic stroke
Author(s) -
JOOD K.,
DANIELSON J.,
LADENVALL C.,
BLOMSTRAND C.,
JERN C.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.02950.x
Subject(s) - fibrinogen , haplotype , single nucleotide polymorphism , stroke (engine) , medicine , ischemic stroke , odds ratio , confidence interval , cardiology , bioinformatics , allele , biology , gene , genetics , genotype , ischemia , mechanical engineering , engineering
Summary. Background : Plasma fibrinogen level and fibrin clot structure are heritable traits that may be of importance in the pathogenesis of ischemic stroke. Objectives : 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. Conclusion: 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).