HTR2C haplotypes and antipsychotics-induced weight gain: X-linked multimarker analysis

Vincenzo De Luca*, Daniel J. Müller, Rudi Hwang, Jeffrey A. Lieberman, Jan Volavka, Herbert Y. Meltzer, James L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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)I2-18/(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).

Original languageEnglish (US)
Pages (from-to)463-467
Number of pages5
JournalHuman Psychopharmacology
Issue number7
StatePublished - Oct 2007


  • Antipsychotics
  • HTR2C
  • Haplotype
  • Pharmacogenetics
  • Schizophrenia
  • Weight gain

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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