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 11q23.1-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.
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D003024:Clozapine / Q000627:therapeutic use*; D004252:DNA Mutational Analysis / Q000379:methods; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011985:Receptors, Serotonin / Q000235:genetics*; D044406:Receptors, Serotonin, 5-HT3; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D003024:Clozapine