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Effects of apolipoprotein E genotype on outcome after ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage
  1. N A Martínez-González,
  2. C L M Sudlow
  1. Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
  1. Correspondence to:
 C L M Sudlow
 Division of Clinical Neurosciences, Western General Hospital, Edinburgh EH4 2XU, UK; cathie.sudlow{at}


Background: Rodent models of acute ischaemic stroke and head injury suggest that apolipoprotein E (APOE) genotype influences neuronal repair, regeneration and survival after brain injury. Possession of an APOE ε4 allele is associated with poor outcome after head injury in clinical studies. APOE might therefore influence outcome after acute stroke in humans.

Objective and methods: To comprehensively search, identify, assess and carry out meta-analyses of studies reporting on the association between APOE and the combined outcome of death or dependency, or death alone, several months after ischaemic stroke, intracerebral haemorrhage (ICH) or subarachnoid haemorrhage (SAH).

Results: Main analyses included data from nine studies on 2262 patients (1453 with ischaemic stroke, 199 with ICH and 610 with SAH). Overall, ε4+ genotypes were not significantly associated with risk of death or dependency several months after stroke. However, there was significant heterogeneity between studies, and between the three pathological types of stroke. ε4+ genotypes were associated with increased death or dependency after SAH (relative risk (RR) 1.40, 95% confidence interval (CI) 1.06 to 1.84), with a trend towards a similar association with ICH (RR 1.38, 95% CI 0.99 to 1.92), but not with ischaemic stroke (RR 0.98, 95% CI 0.85 to 1.12). Results were similar for death alone.

Conclusions: APOE may differentially affect outcome after the three main pathological types of stroke. Further, large studies are needed to confirm or refute these findings, and to assess the possibility of an interaction between the effects of APOE and age.

  • APOE, apolipoprotein E gene
  • ICH, intracerebral haemorrhage
  • SAH, subarachnoid haemorrhage

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  • Published Online First 22 August 2006

  • Funding: NAM-G is supported by CONACyT-SEP México. CLMS is supported by a Wellcome Trust Clinician Scientist award.

  • Competing interests: None.

  • Neither funding source had any role in the design, analysis or interpretation of the results of this study, or in the writing of the paper or the decision to submit it for publication.