-759C/T genetic variation of 5HT2C receptor and clozapine-induced weight gain [8] (multiple letters)

Shih Jen Tsai*, Chen Jee Hong, Younger W Y Yu, Ching Hua Lin, Vincenzo S. Basile, Mario Masellis, Vincenzo De Luca, Herbert Y. Meltzer, James L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalLetterpeer-review

149 Scopus citations


Patients:Study 1 investigated 80 patients of an ethnic Han Chinese population, 52 men and 28 women (mean age of 36.7 years [SD 8.4]. Study 2 investigated 80 patients, 45 men and 28 women of whom 58 were white and 22 were black (age not stated) with diagnosed schizophrenia and also treated wit Leponex.

TypeofStudy:The item contains 2 open clinical studies which investigated the relation between 5 hydroxytryptamine 2C receptor (5HT2C) -759C/T genetic variation and Leponex induced weight gain.

DosageDuration:Dosage not stated. Duration: 4 months for study 1 and 6 weeks for study 2.

Indications:160 patients diagnosed with schizophrenia or schizoaffective psychosis.

FreeText:Study 1 measured body weight before and after 4 months of Leponex treatment. Genotyping of 5HT2C -759C/T polymorphism was also done. Study 2 did genotyping by the same method. The authors classified patients as weight gainers (> 7% weight increase) and non-weight gainers (≦ 7% weight increase). They used x2 case-control analysis to compare the two groups for presence or absence of the variant allele (-759T) of the -759C/T polymorphism. Additionally, the authors used parametric ANCOVA analysis to compare the mean change in weight between the different genotypic panels. Correction was done for possible confounding from baseline weight, sex, age, ethnic origin, and response or non-response.

Results:Results of study 1 showed that patients gained a mean of 2.1 kg (SD 4.7), or 4%, of their baseline body weight, after 4 months. The authors saw no association between change in body-mass index (BMI) and carriage of the 5HT2C -759C/T genotype. In analysis of BMI change as the dependent variable, and age, sex, duration of Leponex treatment, baseline BMI, drug dose, and 5HT2C genotype as predictor variables, only initial BMI had a significant effect on BMI change (p = 0.001). Although a higher proportion of patients with the variant genotype exceeded the weight gain cut off criterion of 7% or more than those with the wild type genotype (39 vs 30%), this result was not significant. Results of study 2 showed that the two genotypic panels did not differ significantly for mean weight gain after 6 weeks of Leponex treatment. Similarly there was no association with weight classification (p = 0.41). The authors noted confounding effects for sex and ethnic origin. Hemizygous T allele men gained significantly more weight than hemizygous C allele men. Black men generally gained more weight than white men (5.95 vs 2.71 kg), but genetic association were similar in stratified analysis. Also, genotype frequencies did not differ between white and black patients, which suggests that population stratification biases did not confound the results. Genotype frequencies did not deviate from those expected under Hardy-Weinberg equilibrium.

AdverseEffects:The body weight of each of the 160 patients was found to have increased.

Original languageEnglish (US)
Pages (from-to)1790-1791
Number of pages2
Issue number9347
StatePublished - Nov 30 2002

ASJC Scopus subject areas

  • Medicine(all)


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