Candidate gene polymorphisms for ischemic stroke

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3436-3442
Number of pages7
JournalStroke
Volume40
Issue number11
DOIs
StatePublished - Nov 2009
Externally publishedYes

Fingerprint

Stroke
Single Nucleotide Polymorphism
Genes
Population
Meta-Analysis
Animal Models

Keywords

  • Candidate genes
  • Genetics
  • Ischemic stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Matarin, M., Brown, W. M., Dena, H., Britton, A., De Vrieze, F. W., Brott, T. G., ... Meschia, J. F. (2009). Candidate gene polymorphisms for ischemic stroke. Stroke, 40(11), 3436-3442. https://doi.org/10.1161/STROKEAHA.109.558015

Candidate gene polymorphisms for ischemic stroke. / Matarin, Mar; Brown, W. Mark; Dena, Hernandez; Britton, Angela; De Vrieze, Fabienne Wavrant; Brott, Thomas G.; Brown, Robert D.; Worrall, Bradford B.; Case, L. Douglas; Chanock, Stephen J.; Metter, E. Jeffrey; Ferruci, Luigi; Gamble, Dale; Hardy, John A.; Rich, Stephen S.; Singleton, Andrew; Meschia, James F.

In: Stroke, Vol. 40, No. 11, 11.2009, p. 3436-3442.

Research output: Contribution to journalArticle

Matarin, M, Brown, WM, Dena, H, Britton, A, De Vrieze, FW, Brott, TG, Brown, RD, Worrall, BB, Case, LD, Chanock, SJ, Metter, EJ, Ferruci, L, Gamble, D, Hardy, JA, Rich, SS, Singleton, A & Meschia, JF 2009, 'Candidate gene polymorphisms for ischemic stroke', Stroke, vol. 40, no. 11, pp. 3436-3442. https://doi.org/10.1161/STROKEAHA.109.558015
Matarin M, Brown WM, Dena H, Britton A, De Vrieze FW, Brott TG et al. Candidate gene polymorphisms for ischemic stroke. Stroke. 2009 Nov;40(11):3436-3442. https://doi.org/10.1161/STROKEAHA.109.558015
Matarin, Mar ; Brown, W. Mark ; Dena, Hernandez ; Britton, Angela ; De Vrieze, Fabienne Wavrant ; Brott, Thomas G. ; Brown, Robert D. ; Worrall, Bradford B. ; Case, L. Douglas ; Chanock, Stephen J. ; Metter, E. Jeffrey ; Ferruci, Luigi ; Gamble, Dale ; Hardy, John A. ; Rich, Stephen S. ; Singleton, Andrew ; Meschia, James F. / Candidate gene polymorphisms for ischemic stroke. In: Stroke. 2009 ; Vol. 40, No. 11. pp. 3436-3442.
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abstract = "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.",
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AU - Brown, W. Mark

AU - Dena, Hernandez

AU - Britton, Angela

AU - De Vrieze, Fabienne Wavrant

AU - Brott, Thomas G.

AU - Brown, Robert D.

AU - Worrall, Bradford B.

AU - Case, L. Douglas

AU - Chanock, Stephen J.

AU - Metter, E. Jeffrey

AU - Ferruci, Luigi

AU - Gamble, Dale

AU - Hardy, John A.

AU - Rich, Stephen S.

AU - Singleton, Andrew

AU - Meschia, James F.

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