title: HTR2C haplotypes and antipsychotics-induced weight gain: X-linked multimarker analysis.
abstract: The 5HT2C receptor (HTR2C) has been hypothesized to represent an important modulator in feeding behavior. Evidence was based on the observation that knock-out mice for the HTR2C receptor gene develop obesity and that many antipsychotics (AP) with potent HTR2C antagonism may induce weight gain in susceptible individuals. Pharmacogenetic studies focusing either on the Cys23Ser polymorphism or on the -759C/T promoter polymorphism of the X-linked HTR2C receptor gene revealed significant findings for the -759C/T polymorphism, however, no study has performed haplotype analyses for both polymorphisms.
  
  
  METHODS
  We analyzed three functional polymorphisms (Cys23Ser, -759C/T, and (GT)12-18/(CT) 4-5) of the HTR2C in 139 schizophrenic patients mainly treated with clozapine. Weight gain was assessed over a time course of 6-14 weeks (mean 8.2 weeks).
  
  
  RESULTS
  Single marker and haplotype analysis revealed no significant associations with AP-induced weight gain. The haplotype Long-C-Ser was protective against weight gain, but the number of subjects available for that analysis was small.
  
  
  CONCLUSIONS
  Our pilot study did not detect any significant haplotype conferring risk for antipsychotic-induced weight gain although the statistical model took into account the X-linked heterogeneity and did correct for confounding factors (i.e., ethnicity, medications, clinical response, time of assessment).
authors: Department of Psychiatry, Centre for Addiction and Mental Health, Neurogenetics Section, University of Toronto, Toronto, ON, Canada. Vincenzo_Deluca@camh.net
authors: Vincenzo
authors: V
authors: De Luca
authors: Daniel J
authors: DJ
authors: Müller
authors: Rudi
authors: R
authors: Hwang
authors: Jeffrey A
authors: JA
authors: Lieberman
authors: Jan
authors: J
authors: Volavka
authors: Herbert Y
authors: HY
authors: Meltzer
authors: James L
authors: JL
authors: Kennedy
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D050172:Genes, X-Linked; D006239:Haplotypes; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D003024:Clozapine