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

Karayiorgou, M.
Gogos, J. A.
Galke, B. L.
Wolyniec, P. S.
Nestadt, G.
Kazazian, H. H.
Housman, D. E.
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Published in Biological Psychiatry. 1998, vol. 43, no. 6, p. 425-431
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 AdultBase SequenceCatechol O-Methyltransferase/ geneticsExons/geneticsFemaleGenetic VariationHumansMaleMolecular Sequence DataMutationOligonucleotides/analysisPolymerase Chain ReactionPolymorphism, Single-Stranded ConformationalSchizophrenia/enzymology/ genetics
PMID: 9532347
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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. https://archive-ouverte.unige.ch/unige:8832

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Deposited on : 2010-07-12

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