APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis.

OBJECTIVE: To determine whether a specific apolipoprotein E (APOE) polymorphism is a risk factor for ischemic cerebrovascular disease (CVD; stroke or TIA). BACKGROUND: The APOE epsilon4 allele is overrepresented in AD, atherosclerosis, and ischemic heart disease. In addition, epsilon4 carriers have higher plasma cholesterol levels than non-epsilon4 carriers. METHODS: Using Medline (OVID and PubMed), a search was performed for all studies that examined APOE in ischemic CVD. The authors identified nine case-control studies that were suitable for analysis. RESULTS: There were 926 patients with ischemic stroke or TIAs and 890 age- and sex-matched control subjects. Overall analysis revealed a significantly higher APOE-epsilon4 allelic frequency in affected patients compared with control subjects (0.14 versus 0.09; odds ratio, 1.68; 95% CI, 1.36 to 2.09; p<0.001). There was a significant excess of the epsilon3 allele (0.85 versus 0.80) but not the epsilon2 allele (0.06 versus 0.06) in the control subjects compared with the ischemic CVD patients. Seven studies had data on APOE genotypes. Carriers of epsilon4 were more frequent among ischemic CVD patients than control subjects (27% versus 18%; odds ratio, 1.73; 95% CI, 1.34 to 2.23; p<0.001). CONCLUSIONS: The APOE-epsilon4 allele and carriers of epsilon4 are more frequent among patients with ischemic CVD compared with control subjects. The epsilon2 allele does not appear to be protective for ischemic CVD. These findings imply a role for the APOE genotype in the pathogenesis of some cases of ischemic CVD.