APOE genotype, ethnicity, and the risk of cerebral hemorrhage.
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 (HR(a)) 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.
Tzourio
C
C
INSERM U708, 75651 Paris cedex 13, France. tzourio@chups.jussieu.fr
Arima
H
H
Harrap
S
S
Anderson
C
C
Godin
O
O
Woodward
M
M
Neal
B
B
Bousser
M-G
MG
Chalmers
J
J
Cambien
F
F
MacMahon
S
S
D000368:Aged; D053329:Apolipoprotein E2 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology / Q000208:ethnology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006801:Humans; D015994:Incidence; D038622:Internationality; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012008:Recurrence; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics
D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E