(Stroke. 2000;31:1299.)
© 2000 American Heart Association, Inc.
Original Contributions |
Age-Dependent Association of Apolipoprotein E Genotypes With Stroke Subtypes in a Japanese Rural Population
From the Department of Physiology, School of Medicine (Y.K.), and Department of Epidemiology, Medical Research Institute (Y.K., A.H.C., T.Y., H.T.), Tokyo Medical and Dental University, Tokyo, Japan; Department of Public Health, Osaka City University Medical School, Osaka, Japan (C.D.); and Hokuetsu Hospital, Shibata City, Niigata, Japan (H.S.).
Correspondence to Yoshihiro Kokubo, MD, Department of Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan. E-mail kokubo.epi{at}mri.tmd.ac.jp
Background and Purpose—The association between apolipoprotein E (apoE) polymorphisms and stroke has been controversial. These controversies may be due to inaccurate classification of stroke and differences in age ranges. We investigated the association between apoE genotypes and stroke subtypes (confirmed by CT or MRI findings) by case-control study in a Japanese rural population.
Methods—First-ever-stroke patients (n=322; cerebral infarction, n=201, intracerebral hemorrhage, n=84, and subarachnoid hemorrhage, n=37) aged 40 to 89 years were recruited from Hokuetsu Hospital, Japan. Healthy controls (n=1126) were selected from the general population in the same area. ApoE genotypes were determined by restriction fragment-length polymorphism analysis.
Results—Compared with apoE 
3/3 subjects, 2 carriers had
a 2-fold risk of cerebral infarction (OR 1.9, 95% CI 1.1 to 3.2).
Among cerebral infarction patients, 2 carriers had increased risks
of cortical infarction (OR 2.4, 95% CI 1.3 to 4.6) (an anatomic
subtype) and atherothrombosis (OR 3.9, 95% CI 1.7 to 9.0) and
cardioembolism (OR 4.9, 95% CI 1.6 to 14.4) but not
lacunar infarction (clinical subtypes). ApoE 4 carriers had a
2.5-fold risk of subarachnoid hemorrhage (OR 2.5, 95%
CI 1.1 to 5.4). ApoE 2/2 subjects had an increased risk of
intracerebral hemorrhage (OR 4.4, 95% CI 1.0
to 19.7). ApoE 3/4 subjects showed 
2-fold increased risk of
atherothrombosis (OR 2.1, 95% CI 1.0 to 4.1) and
intracerebral hemorrhage (OR 1.8, 95% CI 1.0
to 3.3). The association between 2 and stroke was accentuated in
subjects aged 70 years or older but not in those aged 40 to 69
years.
Conclusions—Our study suggests that apoE 2 is a risk factor
for atherothrombosis, cardioembolism, and
intracerebral hemorrhage, whereas 4 is a
risk factor for atherothrombosis, intracerebral
hemorrhage, and subarachnoid hemorrhage. The
occurrence of stroke may be affected by interaction between age and
apoE gene polymorphisms.
Key Words: apolipoproteins • genetics • stroke classification • Japan
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