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

Maria Karayiorgou, Joseph A. Gogos, Brandi L. Galke, Paula Wolyniec, Gerald Nestadt, Stylianos E. Antonarakis, Haig H. Kazazian, David E. Housman, Ann E Pulver

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


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 microde-letions and schizophrenia susceptibility.

Original languageEnglish (US)
Pages (from-to)425-431
Number of pages7
JournalBiological psychiatry
Issue number6
StatePublished - Mar 15 1998


  • 22q11
  • Catechol-O-methyl-transferase
  • Deletions
  • Schizophrenia susceptibility
  • Sequence variants

ASJC Scopus subject areas

  • Biological Psychiatry


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