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

Background and Purpose-Several genes involved in the lymphotoxin-alpha 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-alpha cascade (LTA, LGALS2, and PSMA6) is not a major risk factor for IS. (Stroke. 2009; 40: 970-972.)