Weight gain associated with the -759C/T polymorphism of the 5HT2C receptor and olanzapine.
BACKGROUND
Weight gain from atypical antipsychotic use has become a significant problem. Recent reports have liked the -759 polymorphism of the 5HT2C receptor and obesity as well as weight gain from chlorpromazine, risperidone, and clozapine.


OBJECTIVE
To determine associations between weight gain during olanzapine treatment and the -759C/T polymorphism of the 5HT2C receptor gene.


METHODS
This study included 42 acutely ill patients with schizophrenia (DSM-IV). Weekly assessments included Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Negative Symptoms (SANS), and weight measurements. Olanzapine was titrated to a fixed dose (7.5-20 mg/day) for 2-6 weeks. A 24 hr plasma level was obtained at the endpoint visit. Genomic DNA was isolated from a whole blood sample and analyzed for the -759C/T polymorphism of the 5HT2C receptor.


RESULTS
A chi-square analysis was conducted comparing the distribution of T and C alleles in subjects grouped as gaining more or less than 5, 7, and 10% of their baseline weight during treatment with olanzapine. A threshold of 10% was found to be significant. The distribution of T alleles was higher in subjects not gaining 10% of more of their body weight compared who did gain significant weight (11/27 (40.7%) vs. 0/15 (100%), chi2 = 11.805, P = 0.0035).


CONCLUSIONS
Subjects with a T allele of the 5HT2C receptor -759C/T polymorphism may have a lower incidence of weight gain from olanzapine over a 6 week period compared to those with the C allele. These results need to be replicated.
Ellingrod
Vicki L
VL
University of Iowa, College of Pharmacy, Iowa, USA. vicki-ellingrod@uiowa.edu
Perry
Paul J
PJ
Ringold
John C
JC
Lund
Brian C
BC
Bever-Stille
Kristy
K
Fleming
Frank
F
Holman
Timothy L
TL
Miller
Del
D
D000483:Alleles; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000097:blood / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D000077152:Olanzapine; D020641:Polymorphism, Single Nucleotide; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics*
D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D001569:Benzodiazepines; D000077152:Olanzapine