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(Stroke. 2008;39:2211.)
© 2008 American Heart Association, Inc.

Original Contributions

Genetic Factors for Ischemic and Hemorrhagic Stroke in Japanese Individuals

Yoshiji Yamada, MD, PhD; Norifumi Metoki, MD, PhD; Hidemi Yoshida, PhD; Kei Satoh, MD, PhD; Kimihiko Kato, MD, PhD; Takeshi Hibino, MD, PhD; Kiyoshi Yokoi, MD, PhD; Sachiro Watanabe, MD, PhD; Sahoko Ichihara, MD, PhD; Yukitoshi Aoyagi, PhD; Akitomo Yasunaga, PhD; Hyuntae Park, MSc; Masashi Tanaka, MD, PhD Yoshinori Nozawa, MD, PhD

From the Department of Human Functional Genomics (Y.Y., S.I.), Life Science Research Center, Mie University, Tsu, Japan; Department of Internal Medicine (N.M.), Hirosaki Stroke Center, Hirosaki, Japan; Department of Vascular Biology (H.Y., K.S.), Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; Department of Cardiovascular Medicine (K.K., T.H., K.Y.), Gifu Prefectural Tajimi Hospital, Tajimi, Japan; Department of Cardiology (S.W.), Gifu Prefectural General Medical Center, Gifu, Japan; Department of Genomics for Longevity and Health (Y.A., A.Y., H.P., M.T.), Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan; and Gifu International Institute of Biotechnology (Y.N.), Kakamigahara, Japan.

Correspondence to Yoshiji Yamada, MD, PhD, 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

Background and Purpose— Although genetic epidemiologic studies have implicated several genetic variants as risk factors for ischemic or hemorrhagic stroke, the genetic determinants of these conditions remain largely unknown. We performed an association study to identify gene polymorphisms that confer susceptibility to atherothrombotic cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage.

Methods— The study population comprised 3432 unrelated Japanese individuals: 1362 stroke patients (822 with atherothrombotic cerebral infarction, 333 with intracerebral hemorrhage, and 207 with subarachnoid hemorrhage) and 2070 controls. The genotypes for 50 polymorphisms of 38 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.

Results— An initial ² test (false discovery rate <0.05) and subsequent multivariable logistic-regression analysis with adjustment for conventional risk factors (P<0.05) revealed that the –14CT polymorphism (rs1800977) of ABCA1, the AC (rs3027898) and CT (Ser532Leu, rs1059703) polymorphisms of IRAK1, and the GC (Cys2229Ser) polymorphism (rs619203) of ROS1 were significantly associated with atherothrombotic cerebral infarction; that the –428GA polymorphism (rs710968) of LIMK1 was significantly associated with intracerebral hemorrhage; and that the 13989AG (Ile118Val) polymorphism (NC_000007.12) of CYP3A4 was significantly associated with subarachnoid hemorrhage.

Conclusions— Genotypes for ABCA1, IRAK1, and ROS1 may prove useful for assessment of the genetic risk for atherothrombotic cerebral infarction, whereas those for LIMK1 and CYP3A4 may be similarly beneficial in assessment of the genetic risk for intracerebral hemorrhage and subarachnoid hemorrhage, respectively. Validation of these findings will require additional studies with independent subject panels.

Key Words: cerebral infarction • cerebral hemorrhage • subarachnoid hemorrhage • genetic polymorphism • genetics

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