Polymorphisms in inflammatory genes and the risk of ischemic stroke and transient ischemic attack: results of a multilocus genotyping assay.
BACKGROUND
Single-nucleotide polymorphisms (SNPs) in inflammation-related genes have been linked to an increased risk of ischemic stroke. Most of these SNP results have not been replicated, however, and metaanalyses of the effects of inflammation-related genes are rare. We investigated 49 SNPs in 34 genes previously reported to be related to inflammation in our study. We tested 459 patients with acute ischemic stroke or transient ischemic attack and 459 controls individually matched by sex and age.


METHODS
We studied genetic variation by PCR analysis and subsequent hybridization to linear arrays of sequence-specific oligonucleotides. We used univariate conditional logistic regression analysis to test for associations of conventional vascular risk factors and the SNPs with stroke. Variables showing significant differences (P < 0.05) between cases and controls were included in a multivariate model. ROC curves were plotted to assess the contribution of genetic variation to stroke risk in addition to that of conventional risk factors.


RESULTS
Univariate regression analysis revealed 3 SNPs with significant allelic differences between patients and controls, which fulfilled the criteria for further analysis. Only one of these SNPs, the C5 (complement component 5) 2416A>G variant (rs17611), remained significant after the multivariate analysis (odds ratio, 0.585; P = 0.0037). ROC curve analysis revealed no contribution of this genetic variation to stroke risk.


CONCLUSIONS
We found evidence for an association of the 2416A>G polymorphism in the C5 gene with the risk for ischemic stroke. Our data suggest that the C5 gene particularly influences the risk for patients with microangiopathy.
Greisenegger
Stefan
S
Department of Neurology, Institute of Medical Statistics, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria.
Zehetmayer
Sonja
S
Bauer
Peter
P
Endler
Georg
G
Ferrari
Julia
J
Lang
Wilfried
W
Janisiw
Michael
M
Steiner
Lori
L
Cheng
Suzanne
S
Lalouschek
Wolfgang
W
Mannhalter
Christine
C
D000375:Aging; D002545:Brain Ischemia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012372:ROC Curve; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012727:Sex Characteristics; D020521:Stroke / Q000175:diagnosis / Q000235:genetics*