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 ε4 allele is overrepresented in AD, atherosclerosis, and ischemic heart disease. In addition, ε4 carriers have higher plasma cholesterol levels than non-ε4 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-ε4 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 ε3 allele (0.85 versus 0.80) but not the ε2 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 ε4 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-ε4 allele and carriers of ε4 are more frequent among patients with ischemic CVD compared with control subjects. The ε2 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.