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The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology.

Journal article
Authors Robin Lemmens
Ian Buysschaert
Veerle Geelen
Israel Fernandez-Cadenas
Joan Montaner
Helena Schmidt
Reinhold Schmidt
John Attia
Jane Maguire
Christopher Levi
Katarina Jood
Christian Blomstrand
Christina Jern
Marcin Wnuk
Agniezska Slowik
Diether Lambrechts
Vincent Thijs
Published in Stroke; a journal of cerebral circulation
Volume 41
Issue 9
Pages 1850-7
ISSN 1524-4628
Publication year 2010
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Pages 1850-7
Language en
Links dx.doi.org/10.1161/STROKEAHA.110.58...
Keywords Alleles, Atrial Fibrillation, complications, genetics, Australia, Brain Ischemia, complications, genetics, Europe, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Odds Ratio, Stroke, complications, genetics
Subject categories Medical and Health Sciences

Abstract

BACKGROUND AND PURPOSE: Genome-wide association studies recently identified 2 variants on chromosome 4q25 as susceptibility factors for atrial fibrillation. Interestingly, these variants were subsequently also shown to be associated with stroke. However, it remains unclear whether 4q25 associates with all the stroke subtypes or with cardioembolic stroke in particular, which is often attributable to atrial fibrillation. METHODS: We performed a large case-control association study in 4199 ischemic stroke patients, all subtyped according to Trial of Org 10172 in Acute Stroke Treatment criteria, and 3750 controls derived from 6 studies conducted in Australia, Austria, Belgium, Poland, Spain, and Sweden. Two variants on chromosome 4q25, rs1906591 and rs10033464, were genotyped. RESULTS: Within cases, the A-allele of rs1906591 was associated with atrial fibrillation (odds ratio, 1.64 [95% CI, 1.43 to 1.90]; P=9.2 . 10(-12)), whereas rs10033464 was only marginally associated. There was an association between overall ischemic stroke and rs1906591 (odds ratio, 1.20 [95% CI, 1.09 to 1.32]; P=1.2 . 10(-4)). However, this was probably caused by the large effect of stroke of cardioembolic etiology because no relation was obtained in any other subgroup of stroke. The rs10033464 variant failed to show any relationship with ischemic stroke. CONCLUSIONS: We replicated the association of the rs1906591 variant on chromosome 4q25 with atrial fibrillation and ischemic stroke of cardioembolic etiology. The 4q25 locus failed to associate with noncardiac subtypes of ischemic stroke.

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