title: Prothrombotic gene variation in patients with large and small vessel disease.
abstract: The classification of ischemic stroke into different subtypes is supported in genetic association studies. While several gene variants have been identified as being associated with ischemia subtypes, most studies have not been powered to study subtypes separately. We investigated 887 patients with nondisabling cerebral ischemia of arterial origin and classified ischemia as being caused by large or small vessel disease (LVD or SVD), primarily based on neuroimaging findings. In total, 621 patients had LVD and 266 SVD. The coagulation factor XIII subunit B gene (F13B) His95Arg variant was more common in patients with LVD (mean prevalence difference 9.9%; 95% CI 4.7-15). None of 21 other prothrombotic gene variants was associated with LVD or SVD. Many gene variants may not be specific for one subtype. We could not replicate the genetic associations identified in previous smaller previous studies. Thus claims about genetic associations with specific subtypes of ischemia should be interpreted with caution. The association between F13B His95Arg and LVD requires replication.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: D Martijn O
authors.initials: DM
authors.lastname: Pruissen
authors.forename: L Jaap
authors.initials: LJ
authors.lastname: Kappelle
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001779:Blood Coagulation Factors / Q000235:genetics*; D002545:Brain Ischemia / Q000145:classification / Q000235:genetics*; D015331:Cohort Studies; D005176:Factor XIII / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000145:classification / Q000235:genetics; D014652:Vascular Diseases / Q000145:classification / Q000235:genetics; D055815:Young Adult
chemical_list: D001779:Blood Coagulation Factors; D005176:Factor XIII; C054380:factor XIIIb