Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia

Vicki L Ellingrod; Jeffrey R Bishop; Jessica Moline; Ying-Chi Lin; Del D Miller

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Journal article

Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia

Vicki L Ellingrod, Jeffrey R Bishop, Jessica Moline, Ying-Chi Lin and Del D Miller

Psychopharmacology bulletin, Vol.40(1), pp.57-62

2007

PMID: 17285096

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Abstract

The objective of the current investigation was to determine the relationship between polymorphisms of the leptin system (leptin gene and leptin receptor) and olanzapine-induced weight gain in persons with schizophrenia. Pharmacogenetic association reanalysis of a longitudinal, open label, six week, fixed dose trial of olanzapine response and adverse effects. Thirty-seven males and females with clinically symptomatic schizophrenia (age, 23-52) meeting DSM-IV criteria. Baseline and endpoint weight, BMI, olanzapine dose, plasma levels, and psychopathology measures were completed in a prior study. These subjects were subsequently genotyped for the -1548 G/A polymorphism of the leptin gene and the Q223R polymorphism of the leptin receptor. The relationship between alleles at each locus, olanzapine plasma levels, and percent change in body mass index (BMI) from baseline were conducted. Genotypes and alleles for each locus were not individually associated with olanzapine-induced weight gain in this study population. Changes in BMI from baseline increased significantly in persons with olanzapine plamsa levels >20.6 ng/mL for subjects carrying at least one G allele at both candidate loci compared to those who did not have a G allele at each (P = 0.049). This study suggests that genetic variability in the leptin gene and leptin receptor may predispose some individuals to excessive weight gain from increased exposure to olanzapine.

Antipsychotic Agents - adverse effects

Humans

Middle Aged

Male

Schizophrenia - genetics

Antipsychotic Agents - therapeutic use

Adult

Female

Weight Gain - drug effects

Body Mass Index

Receptors, Leptin

Promoter Regions, Genetic

Genetic Predisposition to Disease - genetics

Pharmacogenetics

Schizophrenia - blood

Genotype

Benzodiazepines - pharmacokinetics

Leptin - genetics

Antipsychotic Agents - pharmacokinetics

Alleles

Polymorphism, Single Nucleotide - genetics

Weight Gain - genetics

Benzodiazepines - adverse effects

Schizophrenia - drug therapy

Benzodiazepines - therapeutic use

Longitudinal Studies

Receptors, Cell Surface - genetics

Details

Title: Subtitle: Leptin and leptin receptor gene polymorphisms and increases in body mass index (BMI) from olanzapine treatment in persons with schizophrenia
Creators: Vicki L Ellingrod - Department of Psychiatry in the University of Michigan College of Pharmacy and College of Medicine, Ann Arbor, Michigan 48109, USA. vellingr@umich.edu
Jeffrey R Bishop
Jessica Moline
Ying-Chi Lin
Del D Miller
Resource Type: Journal article
Publication Details: Psychopharmacology bulletin, Vol.40(1), pp.57-62
Publisher: United States
PMID: 17285096
ISSN: 0048-5764
eISSN: 2472-2448
Grant note: K30HL04117-01A1 / NHLBI NIH HHS K08 MH64158 / NIMH NIH HHS
Language: English
Date published: 2007
Academic Unit: Psychiatry
Record Identifier: 9984003917302771

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