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(Stroke. 2009;40:970.)
© 2009 American Heart Association, Inc.

Research Letters

Genetic Variation in the Lymphotoxin-Alpha Pathway and the Risk of Ischemic Stroke in European Populations

Tobias Freilinger, MD; Steve Bevan, PhD; Stephan Ripke, MD; Andreas Gschwendtner, MD; Peter Lichtner, PhD; Bertram Müller-Myhsok, MD; H. -Erich Wichmann, PhD; Hugh S. Markus, FRCP; Thomas Meitinger, MD, PhD Martin Dichgans, MD

From the Department of Neurology (T.F., A.G., M.D.), Ludwig-Maximilians-Universität, Klinikum Grosshadern, Munich, Germany; the Centre for Clinical Neuroscience (S.B., H.S.M.), St. George’s, University of London, UK; Max-Planck-Institute of Psychiatry (S.R., B.M.-M.), Munich, Germany; the Institute of Human Genetics (P.L., T.M.), HelmholtzZentrum münchen, Munich/Neuherberg, Germany; the Institute of Epidemiology (H.-E.W.), HelmholtzZentrum münchen, Munich/Neuherberg, Germany; IBE, Chair of Epidemiology (H.-E.W.), Ludwig-Maximilians-Universität, Munich, Germany; and the Institute of Human Genetics (T.M.), Technical University Munich, Germany.

Correspondence to Dr Tobias M. Freilinger, Neurologische Klinik und Poliklinik, Klinikum Großhadern, Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 München, Germany. E-mail tobias.freilinger{at}med.uni-muenchen.de

Background and Purpose— Several genes involved in the lymphotoxin- cascade (LTA, LGALS2, and PSMA6) have been linked with the risk of myocardial infarction. Here, we present a comprehensive analysis of these genes in patients with ischemic stroke (IS).

Methods— Twenty-three single nucleotide polymorphisms (SNPs) from LTA, LGALS2, and PSMA6 were genotyped in 601 German IS patients and 736 matched controls. SNPs and haplotypes were tested for association with overall IS, large vessel stroke, and cardioembolic stroke. Significant associations were replicated in an independent sample of 843 IS cases and 933 controls from the UK.

Results— Only one SNP (rs1048990 in PSMA6) showed association with overall IS, but this was not replicated in the UK sample. Three SNPs showed significant associations with stroke subtypes (P<0.05), but none of these associations could be replicated in the UK population.

Conclusions— Genetic variation in the lymphotoxin- cascade (LTA, LGALS2, and PSMA6) is not a major risk factor for IS.

Key Words: stroke • genetics • PSMA6 • LTA • LGALS2