en
Scientific article
English

Identification of sequence variants and analysis of the role of the catechol-O-methyl-transferase gene in schizophrenia susceptibility

Published inBiological psychiatry, vol. 43, no. 6, p. 425-431
Publication date1998
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.

Keywords
  • Adult
  • Base Sequence
  • Catechol O-Methyltransferase/ genetics
  • Exons/genetics
  • Female
  • Genetic Variation
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotides/analysis
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Schizophrenia/enzymology/ genetics
Citation (ISO format)
KARAYIORGOU, M. et al. Identification of sequence variants and analysis of the role of the catechol-O-methyl-transferase gene in schizophrenia susceptibility. In: Biological psychiatry, 1998, vol. 43, n° 6, p. 425–431.
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ISSN of the journal0006-3223
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