Genetic variants in the C-reactive protein gene are associated with microangiopathic ischemic stroke.
OBJECTIVE
C-reactive protein (CRP) is an independent risk factor for cardiovascular disease and ischemic stroke. CRP serum levels are influenced by genetic variation in the CRP gene. Studies investigating the relationship between ischemic stroke and polymorphisms in the CRP gene produced equivocal results. Here we investigate single-nucleotide polymorphisms (SNPs) in the CRP gene in a large German ischemic stroke sample.


METHODS
In a case-control design, 1,669 patients with ischemic stroke due to large-artery atherosclerosis, cardioembolism or cerebral microangiopathy were genotyped for 4 haplotype tagging SNPs (rs3093075, rs1205, rs1130864 and rs1800947) in the CRP gene which have been shown to influence CRP serum concentrations. Geographically matched controls were drawn from 2 prospective population-based studies, the Dortmund Health Study and the Study of Health in Pomerania. The genetic association between the SNPs and stroke was assessed using SNP and haplotype approaches. Results were adjusted for covariates by logistic regression.


RESULTS
All 4 CRP SNPs reside in one linkage disequilibrium block. None of the SNPs or SNP haplotypes were associated with ischemic stroke as a whole. Three SNPs (rs3093075, rs1130864 and rs1800947) showed a significant association with microangiopathic stroke. A common 4-SNP haplotype was protective while 2 rarer haplotypes conferred susceptibility to microangiopathic stroke. All associations remained significant after adjustment for sex, age, hypertension, diabetes mellitus and hypercholesterolemia and after correction for multiple testing using the 'false discovery rate' method.


CONCLUSIONS
Genetic variation in the CRP gene is associated with microangiopathic but not macroangiopathic or cardioembolic stroke in a large German stroke sample.
Kuhlenbaeumer
Gregor
G
Department of Neurology, Leibniz Institute for Atherosclerosis Research, University of Muenster, Muenster, Germany. g.kuhlenbaeumer@neurologie.uni-kiel.de
Huge
Andreas
A
Berger
Klaus
K
Kessler
Christof
C
Voelzke
Henry
H
Funke
Harald
H
Stoegbauer
Florian
F
Stoll
Monika
M
Ringelstein
E Bernd
EB
D000368:Aged; D002097:C-Reactive Protein / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005858:Germany; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D055806:Microvessels; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020521:Stroke / Q000208:ethnology / Q000209:etiology* / Q000235:genetics*; D057049:Thrombotic Microangiopathies / Q000150:complications; D014652:Vascular Diseases / Q000150:complications*
D002097:C-Reactive Protein