HTR2C haplotypes and antipsychotics-induced weight gain: X-linked multimarker analysis.
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).
De Luca
Vincenzo
V
Department of Psychiatry, Centre for Addiction and Mental Health, Neurogenetics Section, University of Toronto, Toronto, ON, Canada. Vincenzo_Deluca@camh.net
Müller
Daniel J
DJ
Hwang
Rudi
R
Lieberman
Jeffrey A
JA
Volavka
Jan
J
Meltzer
Herbert Y
HY
Kennedy
James L
JL
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*
D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D003024:Clozapine