Received on June 9, 2008
Accepted on October 28, 2008

Molecular Diagnostics and Genetics

Polymorphisms in Inflammatory Genes and the Risk of Ischemic Stroke and Transient Ischemic Attack: Results of a Multilocus Genotyping Assay

¹ Department of Neurology, Medical University Vienna, Vienna, Austria
² Institute of Medical Statistics, Medical University Vienna, Vienna, Austria
³ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria
⁴ Department of Neurology, Hospital Barmherzige Brueder, Vienna, Austria
⁵ Department of Department of Human Genetics, Roche Molecular Systems, Inc., Pleasanton, CA

^* To whom correspondence should be addressed. E-mail: christine.mannhalter{at}meduniwien.ac.at.

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 a study of 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 and 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.