title: Polymorphisms of the leptin and HTR2C genes and clozapine-induced weight change and baseline BMI in patients with chronic schizophrenia.
abstract: OBJECTIVE
  We investigated the associations of the LEP-2548A/G and HTR2C-759C/T polymorphisms with long-term clozapine-induced weight changes and baseline BMI in chronic patients with schizophrenia.
  
  
  METHODS
  A total of 113 patients receiving clozapine for at least 1 year were enrolled. Body weight was measured cross-sectionally and data on body weight just before starting clozapine were retrospectively extracted from medical records.
  
  
  RESULTS
  Clozapine-induced change in BMI was correlated inversely with the baseline BMI (P<0.001, ρ=-0.347). The LEP-2548A/G polymorphism was associated significantly with the change in BMI (F=4.380, P=0.015) during clozapine use; those with the AA genotype had the highest BMI gain (1.4±3.1 kg/m), followed by those with the AG (-0.2±3.3 kg/m) and GG (-1.6±3.4 kg/m) genotypes. We also found a significant association between the leptin genotype and BMI at baseline (F=3.499, P=0.034); those with the AA genotype had the lowest baseline BMI (23.4±4.3 kg/m), followed by those with the AG (24.1±4.4 kg/m) and GG (28.8±7.3 kg/m) genotypes. In the case of the HTR2C-759C/T polymorphism, we found a trend in which T alleles were more prevalent in male patients with up to 7% increase in BMI than in those with a greater than 7% increase in BMI [12/54 (22.7%) vs. 1/27 (3.7%); Fisher's exact test: P=0.051].
  
  
  CONCLUSIONS
  This study shows an inverse correlation between the baseline BMI and change in BMI during long-term clozapine use in patients with schizophrenia, and the LEP-2548A/G polymorphism was associated significantly with both these measures.
authors.affiliation: Departments of aPsychiatry bMental Health Research, Seoul National Hospital cDepartment of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Shi Hyun
authors.initials: SH
authors.lastname: Kang
authors.forename: Jong-il
authors.initials: JI
authors.lastname: Lee
authors.forename: Hye Ree
authors.initials: HR
authors.lastname: Han
authors.forename: Minah
authors.initials: M
authors.lastname: Soh
authors.forename: Jin Pyo
authors.initials: JP
authors.lastname: Hong
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015992:Body Mass Index; D002908:Chronic Disease; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy*; D015430:Weight Gain
chemical_list: D014150:Antipsychotic Agents; D020738:Leptin; D044405:Receptor, Serotonin, 5-HT2C; D003024:Clozapine