title: Identification of sequence variants and analysis of the role of the catechol-O-methyl-transferase gene in schizophrenia susceptibility.
abstract: BACKGROUND
  Deletions of 1.5-2 MB of chromosome 22q11 have been previously associated with schizophrenia. The deleted region includes proximally the region harboring genes involved in DiGeorge and velocardiofacial syndromes. Distally, it includes the gene for catechol-O-methyl-transferase (COMT), an enzyme that catalyzes the O-methylation of catecholamine neurotransmitters, including dopamine, and which therefore is considered a candidate gene for schizophrenia.
  
  
  METHODS
  We address the issue of a direct involvement of the COMT gene in the development of schizophrenia by employing the first extensive mutational analysis of this gene in a sample of 157 schizophrenia patients and 129 healthy controls, using single-strand conformation polymorphism and chemical cleavage methodologies.
  
  
  RESULTS
  No mutations were found, but several sequence variants were identified, including the genetic polymorphism that underlies the high/low activity of the enzyme (a Val158-->Met change, which results in the creation of an NlaIII restriction site in the low-activity allele). The distribution of the NlaIII genotypes among subsets of schizophrenia patients was analyzed.
  
  
  CONCLUSIONS
  The results presented here argue against a major role of COMT in schizophrenia in general (although a minor effect could not be excluded) and represent a first step toward a more refined delineation of the phenotype/genotype relationship between 22q11 microdeletions and schizophrenia susceptibility.
authors.affiliation: Rockefeller University, New York, New York 10021, USA.
authors.forename: M
authors.initials: M
authors.lastname: Karayiorgou
authors.forename: J A
authors.initials: JA
authors.lastname: Gogos
authors.forename: B L
authors.initials: BL
authors.lastname: Galke
authors.forename: P S
authors.initials: PS
authors.lastname: Wolyniec
authors.forename: G
authors.initials: G
authors.lastname: Nestadt
authors.forename: S E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: H H
authors.initials: HH
authors.lastname: Kazazian
authors.forename: D E
authors.initials: DE
authors.lastname: Housman
authors.forename: A E
authors.initials: AE
authors.lastname: Pulver
mesh_terms: D000328:Adult; D001483:Base Sequence; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009841:Oligonucleotides / Q000032:analysis; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics*
chemical_list: D009841:Oligonucleotides; D002394:Catechol O-Methyltransferase