Influence of serotonin 3A and 3B receptor genes on clozapine treatment response in schizophrenia

Pharmacogenet Genomics. 2010 Apr;20(4):274-6. doi: 10.1097/FPC.0b013e328337ce3e.

Abstract

Earlier results suggest a minor role of variants in the serotonin 3 receptor (HTR3) subunit genes on antipsychotic treatment outcome of schizophrenia patients. In this study, we further investigated the role of the subunits A and B of the HTR3 receptor using 140 schizophrenia patients taking clozapine for 6 months. We have found significant allelic association of clozapine response with three variants in the HTR3A receptor (rs2276302, rs1062613, rs1150226) although only rs1062613 association remained significant after permutations (permutated P=0.041). Moreover, rs2276302 and rs1062613 have shown nominally significant genotypic association. The two haplotypes composed of rs2276302-rs1062613-rs1150226 were also nominally significant. Taken together, our results suggest that variants in the HTR3A receptor gene can play a role in the treatment outcome of clozapine in schizophrenia patients that are refractory or intolerant of typical antipsychotic therapy. Further studies are necessary to confirm the reported associations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antipsychotic Agents / therapeutic use*
  • Clozapine / therapeutic use*
  • Drug Resistance / genetics
  • Female
  • Genetic Variation
  • Humans
  • Male
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Receptors, Serotonin, 5-HT3 / genetics*
  • Schizophrenia / drug therapy*
  • Schizophrenia / genetics*
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • HTR3A protein, human
  • HTR3B protein, human
  • Receptors, Serotonin, 5-HT3
  • Clozapine