Abstract 4577: Genetic Factors for Ischemic and Hemorrhagic Stroke in Japanese Individuals
Although genetic epidemiological studies have implicated several genetic variants as risk factors for ischemic or hemorrhagic stroke, the genetic determinants of these conditions remain largely unknown. Our goal was to identify gene variants that confer susceptibility to atherothrombotic cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage. The study population comprised 3432 unrelated Japanese individuals: 1362 stroke patients [822 with atherothrombotic cerebral infarction (484 men, 338 women), 333 with intracerebral hemorrhage (213 men, 120 women), and 207 with subarachnoid hemorrhage (83 men, 124 women)] and 2070 controls (881 men, 1189 women). The genotypes for 50 polymorphisms of 38 candidate genes were determined. An initial chi-square test (false discovery rate <0.05) and subsequent multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hypercho-lesterolemia (P <0.05) revealed that the -14C/T polymorphism (rs1800977) of the ATP-binding cassette, sub-family A, member 1 gene (ABCA1), the A/C (rs3027898) and C/T (Ser532Leu, rs1059703) polymorphisms of the interleukin-1 receptor-associated kinase 1 gene (IRAK1), and the G/C (Cys2229Ser) polymorphism (rs619203) of the c-ros oncogene 1, receptor tyrosine kinase gene (ROS1) were significantly associated with atherothrombotic cerebral infarction, that the -428G/A polymorphism (rs710968) of the LIM domain kinase 1 gene (LIMK1) was significantly associated with intracerebral hemorrhage, and that the 13989A/G (Ile118Val) polymorphism (NC 000007.12) of the cytochrome P450, family 3, subfamily A, polypeptide 4 gene (CYP3A4) was significantly associated with subarachnoid hemorrhage. The polymorphisms of IRAK1 and LIMK1 were each in strong linkage disequilibrium. 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.