5-HT2C receptor gene polymorphisms associated with antipsychotic drug action alter promoter activity

Polymorphisms within the 5-HT2C receptor gene promoter have been associated with several physiological and psychiatric phenotypes. Notably, the -759T allele has been associated with resistance to antipsychotic induced weight gain. This study assessed the activity of four promoter haplotypes expressed as luciferase constructs in the SH-SY5Y human neuroblastoma cell line in the presence or absence of a constitutively active 5-HT2C receptor. The presence of either-759T or-697C alleles reduced promoter activity. in addition a haplotype associated with resistance to antipsychotic induced weight showed under activity compared to the most common haplotype. In the presence of the 5-HT2C receptor a similar pattern of promoter activity was observed. Both -759G/T and -697G/G polymorphic sites are likely to play a role in basal promoter activity. Resistance to weight gain may, in part, be mediated by the consequences of reduced 5-HT2C receptor expression. (c) 2007 Elsevier B.V. All rights reserved.