Novel mutations in 5-HT3A and 5-HT3B receptor genes not associated with clozapine response

Clozapine is a potent antagonist of 5-HT3 receptors, which are ligand-gated ion channels that mediate rapid excitatory responses in the central nervous system. Two different isoforms of 5-HT3 receptor subunit genes ( HTR3A and HTR3B) have been identified. They have been assigned to chromosome 11q23....

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Bibliographic Details
Published in:Schizophrenia research 2002-11, Vol.58 (1), p.93-97
Main Authors: Gutiérrez, Blanca, Arranz, Marı́a J, Huezo-Diaz, Patricia, Dempster, David, Matthiasson, P, Travis, M, Munro, Janet, Osborne, Sarah, Kerwin, Robert W
Format: Article
Language:English
Subjects:
Antipsychotic Agents - therapeutic use
Biological and medical sciences
Chi-Square Distribution
Clozapine - therapeutic use
Clozapine response
DNA Mutational Analysis - methods
Gene Frequency
Genotype
HTR3A
HTR3B
Humans
Medical sciences
Mutation
Neuropharmacology
Pharmacology. Drug treatments
Polymerase Chain Reaction
Polymorphism, Genetic
Psycholeptics: tranquillizer, neuroleptic
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Receptors, Serotonin - genetics
Receptors, Serotonin, 5-HT3
Schizophrenia
Schizophrenia - drug therapy
Schizophrenia - genetics
Treatment Outcome
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Summary:Clozapine is a potent antagonist of 5-HT3 receptors, which are ligand-gated ion channels that mediate rapid excitatory responses in the central nervous system. Two different isoforms of 5-HT3 receptor subunit genes ( HTR3A and HTR3B) have been identified. They have been assigned to chromosome 11q23.1–q23.2, a region which in the past has been linked to schizophrenia and bipolar disorder. In this study, we performed a systematic mutation screening of the 5-HT3A and 5-HT3B receptor genes and tested the variants for association with clozapine response in a sample of 266 clozapine-treated patients. Two polymorphisms at the 5-HT3A gene and five new variants in the 5-HT3B gene were finally detected. Of these, only the more frequent mutations (178-C/T and 1596-A/G in 5-HT3A and a CA-repeat in 5-HT3B) were genotyped in our clozapine sample. Association analysis showed similar allele and genotype distributions among clozapine responders and nonresponders. These results make unlikely the possibility that 5-HT3A and 5-HT3B receptor genes underlie variation in clinical response to clozapine. However, the promoter regions of both genes have yet to be investigated.
ISSN:0920-9964
1573-2509
DOI:10.1016/S0920-9964(02)00205-0