1. Low gene expression conferred by association of an allele of the 5-HT2C receptor gene with antipsychotic-induced weight gain.
- Author
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Buckland PR, Hoogendoorn B, Guy CA, Smith SK, Coleman SL, and O'Donovan MC
- Subjects
- Alleles, Antipsychotic Agents therapeutic use, Body Mass Index, Cell Line, Clozapine therapeutic use, Gene Expression genetics, Genetic Markers, Haplotypes genetics, Humans, Obesity genetics, Phenotype, Polymorphism, Genetic, Polymorphism, Single Nucleotide genetics, Transcription, Genetic genetics, Transfection methods, Weight Gain drug effects, Weight Gain genetics, Antipsychotic Agents adverse effects, Clozapine adverse effects, Obesity chemically induced, Receptor, Serotonin, 5-HT2C genetics, Schizophrenia drug therapy
- Abstract
Objective: Association has been reported between the C allele of a -759C/T polymorphism in the promoter of the 5-HT2C receptor gene (HTR2C) and antipsychotic-induced weight gain, suggesting that polymorphic HTR2C expression influences this phenotype. The authors tested this polymorphism, and other promoter variants, for effects on HTR2C transcription., Method: Six HTR2C promoter haplotypes constructed from four polymorphisms were cloned into a luciferase reporter gene plasmid. Their transcriptional activities were then compared in two human cell lines., Results: All haplotypes containing the -759C allele showed less transcriptional activity than haplotypes containing the -759T allele. The A allele of a -997G/A polymorphism was also associated with reduced expression., Conclusions: These findings suggest that the -759C allele is functional and results in relative underexpression of HTR2C. Reduced expression of HTR2C mRNA may underlie vulnerability to weight gain following antipsychotic treatment.
- Published
- 2005
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