Published Online
on December 29, 2005

A more recent version of this article appeared on February 1, 2006

This Article Full Text (PDF) All Versions of this Article: 37/2/364    most recent 01.STR.0000199065.12908.62v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sudlow, C. Articles by Clark, C. Search for Related Content PubMed PubMed Citation Articles by Sudlow, C. Articles by Clark, C. Related Collections Genetics of Stroke

Submitted on July 21, 2005
Revised on October 3, 2005
Accepted on October 21, 2005

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

Cathie Sudlow DPhil, FRCP^*; Nahara Ananí Martínez González MSc; Jennifer Kim; and Catriona Clark

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.

^* To whom correspondence should be addressed. 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

This article has been cited by other articles:

				J. P. A. Ioannidis Effect of Formal Statistical Significance on the Credibility of Observational Associations Am. J. Epidemiol., August 15, 2008; 168(4): 374 - 383. [Abstract] [Full Text] [PDF]

				L. Paternoster, N. A. Martinez Gonzalez, S. Lewis, and C. Sudlow Association Between Apolipoprotein E Genotype and Carotid Intima-Media Thickness May Suggest a Specific Effect on Large Artery Atherothrombotic Stroke Stroke, January 1, 2008; 39(1): 48 - 54. [Abstract] [Full Text] [PDF]

				L. A. Lanterna, Y. Ruigrok, S. Alexander, J. Tang, F. Biroli, L. T. Dunn, and W. S. Poon Meta-analysis of APOE genotype and subarachnoid hemorrhage: Clinical outcome and delayed ischemia Neurology, August 21, 2007; 69(8): 766 - 775. [Abstract] [Full Text] [PDF]

				H. H. Dietrich Apolipoprotein E in Hypercholesteremia and Beyond Stroke, July 1, 2007; 38(7): 2036 - 2036. [Full Text] [PDF]

				D. K. Arnett, A. E. Baird, R. A. Barkley, C. T. Basson, E. Boerwinkle, S. K. Ganesh, D. M. Herrington, Y. Hong, C. Jaquish, D. A. McDermott, et al. Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease: A Scientific Statement From the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group Circulation, June 5, 2007; 115(22): 2878 - 2901. [Abstract] [Full Text] [PDF]

				R. Lemmens, A. Gorner, M. Schrooten, and V. Thijs Association of Apolipoprotein E {epsilon}2 With White Matter Disease but Not With Microbleeds Stroke, April 1, 2007; 38(4): 1185 - 1188. [Abstract] [Full Text] [PDF]

				M. M. Kuroda, M. E. Weck, J. F. Sarwark, A. Hamidullah, and M. S. Wainwright Association of Apolipoprotein E Genotype and Cerebral Palsy in Children Pediatrics, February 1, 2007; 119(2): 306 - 313. [Abstract] [Full Text] [PDF]

				N A Martinez-Gonzalez and C L M Sudlow Effects of apolipoprotein E genotype on outcome after ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage J. Neurol. Neurosurg. Psychiatry, December 1, 2006; 77(12): 1329 - 1335. [Abstract] [Full Text] [PDF]