BACKGROUND: The association of apolipoprotein E (apoE) polymorphism with interindividual variability of serum lipid concentrations and the initiation and progression of atherosclerosis is inconclusive. This study was performed to explore the associations of apoE with lipid concentrations and ischemic stroke in patients with large artery atherosclerosis (LAA) subgroup or without atherosclerotic vascular lesions (small artery occlusion, SAO) subgroup through a case-control study among the Korean population. METHODS: The ischemic stroke group (n=194) was subdivided into an LAA subgroup (n=112) and a SAO without atherosclerotic lesion subgroup (n=82). An age-matched healthy control group (n=168) was recruited. Serum lipid concentrations were measured and apoE genotypes were determined by real-time PCR and melting curve analysis with the LightCycler (Roche Diagnostics). RESULTS: The frequency of the epsilon4 carriers was significantly higher in the ischemic stroke group (22.7%) than in the control group (11.9%) (P=0.01). However, the frequency of 4 carriers showed no difference between the LAA and SAO subgroups (22.3% vs 23.2%, P=0.89). The adjusted low density lipoprotein cholesterol (LDLc) concentration was significantly higher in ischemic stroke group than in control group (P=0.04), but showed no significant differences in all lipid concentrations between the LAA and SAO subgroups. LDLc concentrations were lower in epsilon2 carriers than in epsilon3 and epsilon4 alleles, but showed no difference between the epsilon4 carriers and epsilon3 allele. CONCLUSIONS: Although there was an association between the epsilon4 allele and ischemic stroke and between the LDLc concentration and ischemic stroke, there was no significant difference in the lipid concentrations and distribution of apoE genotypes between the LAA and SAO subgroups. Therefore, the epsilon4 allele may have different effects on the ischemic stroke that are independent of the atherosclerotic mechanism by high LDLc concentration.