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(Stroke. 2009;40:3436.)
© 2009 American Heart Association, Inc.

Original Contributions

Candidate Gene Polymorphisms for Ischemic Stroke

Mar Matarin, PhD; W. Mark Brown, MA; Hernandez Dena, MS; Angela Britton, MS; Fabienne Wavrant De Vrieze, PhD; Thomas G. Brott, MD; Robert D. Brown, Jr, MD; Bradford B. Worrall, MD, MSc; L. Douglas Case, PhD; Stephen J. Chanock, MD; E. Jeffrey Metter, MD; Luigi Ferruci, MD; Dale Gamble, BS; John A. Hardy, PhD; Stephen S. Rich, PhD; Andrew Singleton, PhD James F. Meschia, MD

From the Molecular Genetics Section (M.M., A.B., A.S.) and the Laboratory of Neurogenetics (H.D., F.W.D.V., A.S.), National Institute on Aging, National Institutes of Health, Bethesda, Md; the Department of Biostatistical Sciences (W.M.B., L.D.C.), Division of Public Health Sciences, Wake Forest University Medical Center, Winston-Salem, NC; the Department of Neurology (T.G.B., D.G., J.F.M.), Mayo Clinic, Jacksonville, Fla; the Department of Neurology (R.D.B.), Mayo Clinic, Rochester, Minn; the Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville, Va; the Advanced Technology Center (S.J.C.), National Cancer Institute, Gaithersburg, Md; the Longitudinal Studies Section (E.J.M., L.F.), Intramural Research Program, National Institute on Aging, Bethesda, Md; the Department of Molecular Neuroscience (J.A.H.), Institute of Neurology, University College London, London, UK; and the Center for Public Health Genomics (S.S.R.), University of Virginia, Charlottesville, Va.

Correspondence to James F. Meschia, MD, Department of Neurology, Mayo Clinic, Jacksonville, FL. E-mail Meschia.James{at}mayo.edu

Background and Purpose— Ischemic stroke (IS) is a multifactorial disorder with strong evidence from twin, family, and animal model studies suggesting a genetic influence on risk and prognosis. Several candidate genes for IS have been proposed, but few have been replicated. We investigated the contribution of 67 candidate genes (369 single nucleotide polymorphisms [SNPs]) on the risk of IS in a North American population of European descent.

Methods— Two independent studies were performed. In the first, 342 SNPs from 52 candidate genes were genotyped in 307 IS cases and 324 control subjects. The SNPs significantly associated with IS were tested for replication in another cohort of 583 IS cases and 270 control subjects. In the second study, 212 SNPs from 62 candidate genes were analyzed in 710 IS cases with subtyping available and 3751 control subjects.

Results— None of the candidate genes (SNPs) were significantly associated with IS risk independent of known stroke risk factors after correction for multiple hypotheses testing.

Conclusion— These results are consistent with previous meta-analyses that demonstrate an absence of genetic association of variants in plausible candidate genes with IS risk. Our study suggests that the effect of the investigated SNPs may be weak or restricted to specific populations or IS subtypes.

Key Words: candidate genes • genetics • ischemic stroke