Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis

Weight gain, leading to further morbidity and poor treatment adherence, is a common consequence of treatment with antipsychotic drugs. Two recent studies in the same cohort of Chinese Han subjects have shown that polymorphisms of the promoter regions of both the serotonin 5-hydroxytryptamine 2C (5-H...

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Bibliographic Details
Published in:Pharmacogenetics and genomics Vol. 15; no. 4; p. 195
Main Authors: Templeman, Lucy A, Reynolds, Gavin P, Arranz, Belen, San, Luis
Format: Journal Article
Language:English
Published: United States 01.04.2005
Subjects:
Adult
Affective Disorders, Psychotic - complications
Affective Disorders, Psychotic - drug therapy
Alleles
Antipsychotic Agents - adverse effects
Antipsychotic Agents - pharmacology
Benzodiazepines - pharmacology
Body Mass Index
Female
Genetic Variation
Genotype
Humans
Leptin - blood
Leptin - genetics
Male
Models, Genetic
Olanzapine
Pharmacogenetics
Polymorphism, Genetic
Promoter Regions, Genetic
Receptor, Serotonin, 5-HT2C - genetics
Receptors, Leptin
Schizophrenia - drug therapy
Time Factors
Weight Gain - drug effects
Weight Gain - genetics
ISSN:1744-6872
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Summary:Weight gain, leading to further morbidity and poor treatment adherence, is a common consequence of treatment with antipsychotic drugs. Two recent studies in the same cohort of Chinese Han subjects have shown that polymorphisms of the promoter regions of both the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor and the leptin genes, are associated with antipsychotic-induced weight gain over 10 weeks. We have investigated whether these effects remain true in a Caucasian population and following longer term treatment. Seventy-three Spanish caucasian patients with a first-episode psychosis and initially drug-naive were genotyped for the 5-HT2C receptor -759C/T and leptin -2548A/G polymorphisms. Body mass index and plasma leptin levels were monitored after 6 weeks, 3 months and 9 months of antipsychotic treatment. Patients with the -759T variant allele showed significantly less weight gain than those without this allele. This effect held true in the smaller group of patients receiving olanzapine. The -2548 leptin polymorphism was not associated with short-term (6 week and 3 month) weight increases but did show significant association with 9-month antipsychotic-induced weight gain. The 5-HT2C -759 genotype was significantly associated with pre-treatment plasma leptin levels. These findings confirm the importance of two genetic factors associated with long-term antipsychotic-induced weight increases in schizophrenia, and implicate a role for leptin in the 5-HT receptor-mediated weight regulation.
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ISSN:1744-6872
DOI:10.1097/01213011-200504000-00002