Age-dependent association of apolipoprotein E genotypes with stroke subtypes in a Japanese rural population

Background and Purpose-The association between apolipoprotein E (apoE) poly morphisms and stroke has been controversial. These controversies may be due to inaccurate classification of stroke and differences in age ranges. We i nvestigated the association between apoE genotypes and stroke subtypes (con firmed by CT or MRI findings) by case-control study in a Japanese rural pop ulation. Methods-First-ever-stroke patients (n=322; cerebral infarction, n=201, intr acerebral hemorrhage, n=84, and subarachnoid hemorrhage, n=37) aged 40 to 8 9 years were recruited from Hokuetsu Hospital, Japan. Healthy controls (n=1 126) were selected from the general population in the same area, ApoE genot ypes were determined by restriction fragment-length polymorphism analysis. Results-Compared with apoE epsilon 3/epsilon 3 subjects, epsilon 2 carriers had a 2-fold risk of cerebral infarction (OR 1.9, 95% CI 1.1 to 3.2), Amon g cerebral infarction patients, epsilon 2 carriers had increased risks of c ortical infarction (OR 2.4, 95% CI 1.3 to 4.6) (an anatomic subtype) and at herothrombosis (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 epsilo n 4 carriers had a 2.5-fold risk of subarachnoid hemorrhage (OR 2.5, 95% CI 1.1 to 5.4). ApoE epsilon 2/epsilon 2 subjects had an increased risk of in tracerebral hemorrhage (OR 4,4, 95% CI 1.0 to 19.7), ApoE epsilon 3/epsilon 4 subjects showed approximate to 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 epsilon 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 epsilon 2 is a risk factor for ath erothrombosis, cardioembolism, and intracerebral hemorrhage, whereas epsilo n 4 is a risk factor for atherothrombosis, intracerebral hemorrhage, and su barachnoid hemorrhage. The occurrence of stroke may be affected by interact ion between age and apoE gene polymorphisms.