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.
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.
Authors: Pieter J Hoekstra; Pieter W Troost; Bertine E Lahuis; Hans Mulder; Erik J Mulder; Barbara Franke; Jan K Buitelaar; George M Anderson; Lawrence Scahill; Ruud B Minderaa Journal: J Child Adolesc Psychopharmacol Date: 2010-12 Impact factor: 2.576
Authors: Marilyn Ader; W Timothy Garvey; Lawrence S Phillips; Charles B Nemeroff; Georges Gharabawi; Ramy Mahmoud; Andrew Greenspan; Sally A Berry; Dominique L Musselman; Jacqueline Morein; Young Zhu; Lian Mao; Richard N Bergman Journal: J Psychiatr Res Date: 2008-02-25 Impact factor: 4.791
Authors: Jian-Ping Zhang; Todd Lencz; Ryan X Zhang; Masahiro Nitta; Lawrence Maayan; Majnu John; Delbert G Robinson; W Wolfgang Fleischhacker; Rene S Kahn; Roel A Ophoff; John M Kane; Anil K Malhotra; Christoph U Correll Journal: Schizophr Bull Date: 2016-05-23 Impact factor: 9.306