title: A polymorphism of the ABCA1 gene confers susceptibility to schizophrenia and related brain changes.
abstract: OBJECTIVE
  The ATP-binding cassette transporter A1 (ABCA1) mediates cellular cholesterol efflux through the transfer of cholesterol from the inner to the outer layer of the cell membrane and regulates extracellular cholesterol levels in the central nervous system. Several lines of evidence have indicated lipid and myelin abnormalities in schizophrenia.
  
  
  METHODS
  Initially, we examined the possible association of the polymorphisms of the ABCA1 gene (ABCA1) with susceptibility to schizophrenia in 506 patients with schizophrenia (DSM-IV) and 941 controls. The observed association was then subject to a replication analysis in an independent sample of 511 patients and 539 controls. We further examined the possible effect of the risk allele on gray matter volume assessed with magnetic resonance imaging (MRI) in 86 patients with schizophrenia (49 males) and 139 healthy controls (47 males).
  
  
  RESULTS
  In the initial association study, the 1587 K allele (rs2230808) was significantly more common in male patients with schizophrenia than in male controls. Although such a significant difference was not observed in the second sample alone, the increased frequency of the 1587 K allele in male patients remained to be significant in the combined male sample of 556 patients and 594 controls. Male schizophrenia patients carrying the 1587 K allele had a smaller amount of gray matter volume than those who did not carry the allele.
  
  
  CONCLUSIONS
  Our data suggest a male-specific association of the 1587 K allele of ABCA1 with susceptibility to schizophrenia and smaller gray matter volume in schizophrenia.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. ota@ncnp.go.jp
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nemoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tatsumi
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Moriguchi
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000328:Adult; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D012737:Sex Factors
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1