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(Stroke. 2006;37:364.)
© 2006 American Heart Association, Inc.

Original Contributions

Does Apolipoprotein E Genotype Influence the Risk of Ischemic Stroke, Intracerebral Hemorrhage, or Subarachnoid Hemorrhage?

Systematic Review and Meta-Analyses of 31 Studies Among 5961 Cases and 17 965 Controls

From the Division of Clinical Neurosciences (C.S., N.A.M.G.), Medical Genetics Section (C.S.), and Medical School (J.K., C.C.), University of Edinburgh, United Kingdom.

Correspondence to Dr Cathie Sudlow, Wellcome Clinician Scientist, Senior Lecturer and Honorary Consultant Neurologist, Division of Clinical Neurosciences, Western General Hospital, Edinburgh, EH4 2XU, UK. E-mail cathie.sudlow{at}ed.ac.uk

Background and Purpose— Apolipoprotein E genotype (APOE) is associated with cholesterol metabolism, ischemic heart disease, and cerebral amyloid angiopathy, and so may affect risk of both ischemic and hemorrhagic stroke.

Methods— We comprehensively sought and identified studies of the association of apoE with ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). We did meta-analyses to assess the evidence for an association between APOE and the various pathological types and subtypes of stroke, and assessed the effects of several methodological criteria.

Results— We analyzed data from 31 eligible studies (26 IS, 8 ICH, and 3 SAH) in 5961 cases and 17 965 controls. 4 allele–containing (4+) genotypes were significantly associated with IS (odds ratio [OR], 1.11; 95% CI, 1.01 to 1.22) and SAH (OR, 1.42; 95% CI, 1.01 to 1.99) and nonsignificantly with ICH (OR, 1.16; 95% CI, 0.93 to 1.44), whereas 2+ genotypes were associated with ICH (OR, 1.32; 95% CI, 1.01 to 1.74). Associations appeared stronger with 4+ genotypes for large artery compared with other IS subtypes and for Asian compared with white populations, and with 2+ genotypes for lobar compared with deep hemorrhages. However, we found no association between 4+ genotypes and IS when we analyzed only larger studies (>200 cases; OR, 0.99; 95% CI, 0.88 to 1.11) or studies without control selection bias (OR, 0.99; 95% CI, 0.85 to 1.17).

Conclusions— Publication and selection biases make existing studies of APOE and stroke unreliable. Further, very large, methodologically rigorous studies are needed.

Key Words: apolipoproteins E • genetics • meta-analysis • stroke

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