This Article Full Text Full Text (PDF) All Versions of this Article: 39/5/1586    most recent STROKEAHA.107.502963v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Matarin, M. PubMed PubMed Citation Articles by Matarin, M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Related Collections Genetics of Stroke

(Stroke. 2008;39:1586.)
© 2008 American Heart Association, Inc.

Research Letters

Whole Genome Analyses Suggest Ischemic Stroke and Heart Disease Share an Association With Polymorphisms on Chromosome 9p21

Mar Matarin, PhD; W. Mark Brown, MA; Andrew Singleton, PhD; John A. Hardy, PhD; James F. Meschia, MD for the ISGS investigators

From the Molecular Genetics Unit (M.M., A.S.), Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Porter Neuroscience Research Center, Bethesda, Md; the Section on Biostatistics (W.M.B.), Department of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC; the Reta Lila Weston Institute of Neurological Studies (J.A.H.), Institute of Neurology, University College London, London, UK; and the Department of Neurology (J.F.M.), Mayo Clinic, Jacksonville, Fla.

Correspondence to Mar Matarin, PhD, Molecular Genetics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Porter Neuroscience Research Center, 35 Lincoln Drive, Bethesda, MD 20892. E-mail delmarm{at}mail.nih.gov

Abstract

Background and Purpose— Recently independent studies reported an association between coronary heart disease and single-nucleotide polymorphisms (SNPs) located at chromosome 9p21, near CDKN2A and CDKN2B genes. Given that stroke is a common complication after myocardial infarction, we investigated if the same SNPs were associated with ischemic stroke in our population.

Methods— We recently initiated a whole genome analysis of ischemic stroke and published the first stage of a case control study using >400 000 SNPs from Illumina Infinium Human-1 and HumanHap300 assays. We focused on SNPs recently associated with heart disease by Helgadottir and colleagues and SNPs from the same haplotype block.

Results— In analyses both unadjusted and adjusted for stroke risk factors, significant associations with ischemic stroke were observed for SNPs from the same haplotype block previously associated with myocardial infarction. Significant association was also seen between disease and haplotypes involving these SNPs, both with and without adjustment for stroke risk factors (odd ratios: 1.01 to 2.65).

Conclusions— These data are important for 3 reasons: first, they suggest a genetic association for stroke; second, they suggest that this association shares pathogenic mechanisms with heart disease and diabetes; and third, they illustrate, that public release of data can facilitate rapid risk locus discovery.

Key Words: ischemic stroke • genetics • heart disease • diabetes