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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1920.)
© 2006 American Heart Association, Inc.

Thrombosis

Genetic Risk for Ischemic and Hemorrhagic Stroke

Yoshiji Yamada; Norifumi Metoki; Hidemi Yoshida; Kei Satoh; Sahoko Ichihara; Kimihiko Kato; Takashi Kameyama; Kiyoshi Yokoi; Hitoshi Matsuo; Tomonori Segawa; Sachiro Watanabe; Yoshinori Nozawa

From the Department of Human Functional Genomics (Y.Y., S.I.), Life Science Research Center, Mie University, Tsu, Japan; Gifu International Institute of Biotechnology (Y.Y., Y.N.), Kakamigahara, Japan; Department of Internal Medicine (N.M.), Reimeikyo Rehabilitation Hospital, Minamitsugaru, Japan; Department of Vascular Biology (H.Y., K.S.), Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan; Departments of Cardiovascular Medicine (K.K., K.Y.) and Neurology (T.K.), Gifu Prefectural Tajimi Hospital, Tajimi, Japan; and Department of Cardiology (H.M., T.S., S.W.), Gifu Prefectural Gifu Hospital, Gifu, Japan.

Correspondence to Yoshiji Yamada, MD, PhD, FAHA, Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan. E-mail yamada{at}gene.mie-u.ac.jp

Objective— We performed an association study to identify gene polymorphisms for assessing the genetic risk of ischemic or hemorrhagic stroke.

Methods and Results— The study population comprised 3151 unrelated Japanese individuals: 1141 stroke patients (636 with atherothrombotic cerebral infarction, 282 with intracerebral hemorrhage, and 223 with subarachnoid hemorrhage) and 2010 controls. The genotypes for 202 polymorphisms of 152 genes were determined by suspension array technology. Multivariable logistic regression analysis with adjustment for conventional risk factors revealed that the –572GC polymorphism of the interleukin-6 (IL-6) gene (IL6) was significantly (P<0.001) associated with both atherothrombotic cerebral infarction and intracerebral hemorrhage and that the –55CT polymorphism of the uncoupling protein 3 gene (UCP3), the –863CA polymorphism of the tumor necrosis factor (TNF) gene (TNF), and the GA (Gly243Asp) polymorphism of the polycystic kidney disease 1–like gene (PKD1-like) were significantly associated with subarachnoid hemorrhage.

Conclusions— IL6 genotype may be useful in assessing the genetic risk for atherothrombotic cerebral infarction and intracerebral hemorrhage, and genotypes for UCP3, TNF, and PKD1-like may be similarly beneficial in assessment of the risk for subarachnoid hemorrhage. Validation of our findings will require additional studies with independent subject panels.

The relations of 202 gene polymorphisms to atherothrombotic cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage were examined. Multivariable logistic regression analysis revealed significant associations of IL6 genotype with both atherothrombotic cerebral infarction and intracerebral hemorrhage and of genotypes for UCP3, TNF, and PKD1-like with subarachnoid hemorrhage.

Key Words: atherothrombotic cerebral infarction • intracerebral hemorrhage • subarachnoid hemorrhage • polymorphism • genetics

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