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Variations in FGG and FGA genes appear to contribute to stroke risk
18 August 2008
MedWire News: Variations in common haplotypes of the genes encoding fibrinogen γ and γ (FGG and FGA) appear to influence risk for stroke, according to a substudy of the population-based Rotterdam Study.
In particular, the risk for ischemic stroke was higher in carriers of the FGG and FGA H3 haplotypes than in those with the H1 haplotype of these genes, and the data suggest that an opposite association may be present for hemorrhagic stroke.
A haplotype analysis, such as the one used in this study, may be more accurate in finding associations with risk for stoke than single nucleotide polymorphism (SNP) analysis, say Elim Cheung (Erasmus University Medical Center, Rotterdam, The Netherlands) and colleagues.
Their study, which appears in the journal Thrombosis and Haemostasis, estimated common haplotypes using seven tagging SNPs across a 30-kb region containing the FGG and FGA genes.
Elevated total fibrinogen levels are associated with increased risk for ischemic heart disease and stroke, but it is unclear whether fibrinogen is a marker or is causally involved in stroke. The current study sought to determine the association between common genetic variations in FGG and FGA, which are involved with fibrinogen and fibrin clot structure, and risk for stroke.
The 6275 participants (59% women) were aged 55 years or over, with a median age of 68 years, and free from stroke at baseline. They were assessed for at least one FGG or FGA SNP.
During an average 10.1 years of follow-up, 668 strokes were reported; 393 were classified as ischemic, 62 as hemorrhagic, and 213 were unspecified.
FGG and FGA H3 was associated with an increased risk for ischemic stroke, at an odds ratio (OR) of 1.36, and a reduced likelihood for hemorrhagic stroke, at an OR of 0.71, compared with the most frequent haplotype (H1).
No association with stroke was found when the two genes were analyzed separately.
"This finding [the relationship of FGG and FGA-Haplotype 3 and risk of ischemic stroke] strengthens the hypothesis that fibrin structure may be a causal factor in the development of stroke," say the authors.
