Association of clozapine-induced weight gain with a polymorphism in the leptin promoter region in patients with chronic schizophrenia in a Chinese population

J Clin Psychopharmacol. 2007 Jun;27(3):246-51. doi: 10.1097/jcp.0b013e3180582412.


Weight gain is a problem commonly encountered with antipsychotic treatment and has become more apparent with increasing use of the newer atypical antipsychotics. The adipocyte-derived hormone, leptin, has been associated with body weight and energy homeostasis, and abnormal regulation of leptin could play a role in weight gain induced by antipsychotics. We investigated whether a leptin gene promoter variant affected weight gain after long-term treatment with clozapine in chronic schizophrenia. Leptin G2548A polymorphism was genotyped in 102 Chinese Han inpatients with chronic schizophrenia treated with clozapine. Weight gains, expressed as change in body mass index (BMI), were monitored after long-term clozapine treatment. We found a significant relationship between the 3 leptin G/A genotypes and mean BMI gain (F(2,99) = 3.35, P = 0.039, r(2) = 0.09). Moreover, genotype had a strong effect on BMI gain in male (P = 0.004, r(2) = 0.16), but not in female patients (P > 0.05). Thus, variation in the leptin gene may be a risk factor for weight gain in male patients with schizophrenia on long-term clozapine treatment.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Asian Continental Ancestry Group*
  • Body Mass Index
  • China
  • Chronic Disease
  • Clozapine / adverse effects*
  • Clozapine / therapeutic use
  • Female
  • Genotype
  • Humans
  • Leptin / blood
  • Leptin / genetics*
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic
  • Schizophrenia / drug therapy*
  • Weight Gain / drug effects*
  • Weight Gain / genetics


  • Antipsychotic Agents
  • Leptin
  • Clozapine