title: Association ofTOMM40andSLC22A4polymorphisms with ischemic stroke.
abstract: Recent genome-wide association studies (GWASs) and their meta-analyses have identified various genes and loci underlying the predisposition to ischemic stroke or coronary artery disease in Caucasian populations. Given that ischemic stroke and coronary artery disease may have a shared genetic architecture, certain polymorphisms may confer genetic susceptibility to these two diseases. The aim of the present study was to examine the possible association of ischemic stroke with 29 single-nucleotide polymorphisms (SNPs) previously identified by the meta-analyses of GWASs as susceptibility loci for coronary artery disease. The study population comprised 3,187 Japanese individuals, including 894 subjects with ischemic stroke and 2,293 controls. The genotypes for the 29 SNPs of the 28 genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2test between subjects with ischemic stroke and controls revealed that rs9319428 (G→A) of the fms-related tyrosine kinase 1 gene (P=0.0471), rs2075650 (G→A) of the translocase of outer mitochondrial membrane 40 homolog gene (TOMM40, P=0.0102) and rs273909 (T→C) of the solute carrier family 22, member 4 gene (SLC22A4, P=0.0097) were significantly (P<0.05) associated with the prevalence of ischemic stroke. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, smoking status and the prevalence of hypertension, diabetes mellitus and dyslipidemia revealed that rs2075650 ofTOMM40(P=0.0443; recessive model; odds ratio=0.50) and rs273909 ofSLC22A4(P=0.0123; dominant model; odds ratio=0.45) were significantly associated with ischemic stroke with the minor G and C allele, respectively, being protective against this condition.TOMM40andSLC22A4may thus be susceptibility loci for ischemic stroke in Japanese individuals.
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamase
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Horibe
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ueyama
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511-0428, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.affiliation: Department of Cardiology, Kasugai Municipal Hospital, Kasugai, Aichi 486-8510, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.affiliation: Department of Internal Medicine, Meitoh Hospital, Nagoya, Aichi 465-0025, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan.
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
keywords: cerebral infarction; genetic epidemiology; genetics; ischemic stroke; polymorphism