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.
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.
Berger
Klaus
K
Institute of Epidemiology and Social Medicine, University of Muenster, Domagkstr. 3, Muenster 48149, Germany. bergerk@uni-muenster.de
Stögbauer
Florian
F
Stoll
Monika
M
Wellmann
Juergen
J
Huge
Andreas
A
Cheng
Suzanne
S
Kessler
Christof
C
John
Ulrich
U
Assmann
Gerd
G
Ringelstein
E Bernd
EB
Funke
Harald
H
D000368:Aged; D001224:Aspartic Acid / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D007511:Ischemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D019007:P-Selectin / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism; D020521:Stroke / Q000235:genetics*
C515334:CCR2 protein, human; D039421:Integrin alpha2; D018793:Interleukin-13; D019007:P-Selectin; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D001224:Aspartic Acid; D018698:Glutamic Acid; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III