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


METHODS
Pharmacogenetic association reanalysis of a longitudinal, open label, six week, fixed dose trial of olanzapine response and adverse effects.


METHODS
Thirty-seven males and females with clinically symptomatic schizophrenia (age, 23-52) meeting DSM-IV criteria.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Ellingrod
Vicki L
VL
Department of Psychiatry in the University of Michigan College of Pharmacy and College of Medicine, Ann Arbor, Michigan 48109, USA. vellingr@umich.edu
Bishop
Jeffrey R
JR
Moline
Jessica
J
Lin
Ying-Chi
YC
Miller
Del D
DD
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015992:Body Mass Index; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics
D014150:Antipsychotic Agents; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D001569:Benzodiazepines; D000077152:Olanzapine