Human Genetics

, Volume 121, Issue 2, pp 169–178 | Cite as

The glu298asp polymorphism in the nitric oxide synthase 3 gene is associated with the risk of ischemic stroke in two large independent case–control studies

  • Klaus Berger
  • Florian Stögbauer
  • Monika Stoll
  • Juergen Wellmann
  • Andreas Huge
  • Suzanne Cheng
  • Christof Kessler
  • Ulrich John
  • Gerd Assmann
  • E. Bernd Ringelstein
  • Harald Funke
Original Investigation

Abstract

The search for genes involved in the pathogenesis of stroke has been highlighted as a field of needs. We followed the concept, that stroke represents a complex genetic disorder, and analyzed the contribution of 106 informative single nucleotide polymorphisms (SNPs) from 63 candidate genes for cardiovascular diseases for the risk of stroke. We conducted two independent case–control studies in two different German regions and recruited a total of 1,901 hospitalized stroke cases and 1,747 regional population controls. The smaller of both studies was used as the replication study. Multiplex PCR in combination with allele-specific hybridization was used for genotype determination. Descriptive statistics, permutations and multivariable logistic regression were used in the analyses. After permutation testing 5 SNPs, located in the nitric oxide synthase 3, the alpha 2 integrin, the interleukin 13, the selectin P and the chemokine receptor 2 genes, had a significant allele difference between cases and controls in the larger study. For one of these SNPs, the glu298asp polymorphism in the nitric oxide synthase 3 gene, an association with ischemic stroke was replicated in the second study and also in a combined analysis of both studies. This association was independent of age, gender, hypertension, diabetes and hypercholesterolemia in both studies. Using large sample sizes and a replication study approach, we found evidence for a role of a polymorphism in the nitric oxide synthase 3 gene in stroke onset.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Klaus Berger
    • 1
  • Florian Stögbauer
    • 2
    • 8
  • Monika Stoll
    • 6
  • Juergen Wellmann
    • 1
  • Andreas Huge
    • 6
  • Suzanne Cheng
    • 3
  • Christof Kessler
    • 4
  • Ulrich John
    • 5
  • Gerd Assmann
    • 6
  • E. Bernd Ringelstein
    • 2
    • 6
  • Harald Funke
    • 6
    • 7
  1. 1.Institute of Epidemiology and Social MedicineUniversity of MuensterMuensterGermany
  2. 2.Department of NeurologyUniversity of MuensterMuensterGermany
  3. 3.Roche Molecular SystemsAlamedaUSA
  4. 4.Department of NeurologyUniversity of GreifswaldGreifswaldGermany
  5. 5.Institute of Epidemiology and Social MedicineUniversity of GreifswaldGreifswaldGermany
  6. 6.Leibniz Institute of Arteriosclerosis ResearchUniversity of MuensterMuensterGermany
  7. 7.Department of Molecular HaemostaseologyUniversity of JenaJenaGermany
  8. 8.Department of NeurologyKlinikum OsnabrueckOsnabrueckGermany

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