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Published online before print February 6, 2008, doi:10.1212/01.wnl.0000308819.43401.87)
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 Volume 70, Number 16, April 15, 2008
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Received February 11, 2007
Accepted July 2, 2007

APOE genotype, ethnicity, and the risk of cerebral hemorrhage

C. Tzourio MD, PhD*, H. Arima MD, S. Harrap PhD, C. Anderson MD, PhD, O. Godin MSc, M. Woodward PhD, B. Neal PhD, M. -G. Bousser MD, J. Chalmers PhD, F. Cambien MD, PhD, and S. MacMahon PhD

From INSERM U708 (C.T., O.G.), the Department of Neurology, Hôpital Lariboisière (C.T., M.-G.B.), and the Université Pierre et Marie Curie-Paris 6 (C.T., O.G.), Paris, France; The George Institute for International Health (C.T., C.A., M.W., B.N., J.C., S.M.), University of Sydney, Australia; Department of Environmental Medicine (H.A.), Kyushu University, Fukuoka, Japan; Department of Physiology (S.H.), University of Melbourne, Australia; Mt Sinai Medical Center (M.W.), New York, NY; and INSERM U525 (F.C.), Paris, France.


* To whom correspondence should be addressed. E-mail: tzourio{at}chups.jussieu.fr.

Objective: The apolipoprotein E (APOE) polymorphism is an established risk factor for intracerebral hemorrhage (ICH) that is related to cerebral amyloid angiopathy in the white population. Among Asian populations, although ICH represents up to one third of all strokes and has high rates of mortality and morbidity, the role of the APOE polymorphism has not been well studied.

Methods: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial of a blood pressure lowering regimen in subjects with prior cerebrovascular disease. APOE status was determined for 5,671 patients, including 2,148 Asians (38%).

Results: During the 3.9 years of follow-up, ICH occurred in 99 patients. Overall, carrying an {epsilon}2 or {epsilon}4 allele of the APOE polymorphism was associated with an adjusted hazard ratio (HRa) of 1.85 (95% CI = 1.24 to 2.76). In Asian patients the risk of ICH for {epsilon}2 or {epsilon}4 carriers was 2.11 (95% CI = 1.28 to 3.47) and 1.48 (95% CI = 0.76 to 2.87) in Europeans. Carriers of the {epsilon}2 or {epsilon}4 allele had an increased risk of both incident and recurrent ICH, and both cortical and deep ICH, and most risk estimates were higher in Asians than in Europeans. For both ethnic groups and for subtypes of ICH active treatment more than halved the risk of ICH and the treatment effects were not different in carriers of the {epsilon}2 or {epsilon}4 allele and in those with the {epsilon}3{epsilon}3 genotype.

Conclusions: There is a strong association between APOE genotype and the risk of intracerebral hemorrhage (ICH). In Asian patients the role of APOE polymorphisms in ICH is much broader than was previously supposed.






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