title: No evidence for a role of the peroxisome proliferator-activated receptor gamma (PPARG) and adiponectin (ADIPOQ) genes in antipsychotic-induced weight gain.
abstract: Antipsychotics frequently cause changes in glucose metabolism followed by development of weight gain and/or diabetes. Recent findings from our group indicated an influence of glucose-related genes on this serious side effect. With this study, we aimed to extend previous research and performed a comprehensive study on the peroxisome proliferator-activated receptor gamma (PPARG) and the adiponectin (ADIPOQ) genes. In 216 schizophrenic patients receiving antipsychotics for up to 14 weeks, we investigated single-nucleotide polymorphisms in or near PPARG (N=24) and ADIPOQ (N=18). Statistical analysis was done using ANCOVA in SPSS. Haplotype analysis was performed in UNPHASED 3.1.4 and Haploview 4.2. None of the PPARG or ADIPOQ variants showed significant association with antipsychotic-induced weight gain in our combined sample or in a refined subsample of patients of European ancestry treated with clozapine or olanzapine after correction for multiple testing. Similarly, no haplotype association could withstand multiple test correction. Although we could not find a significant influence of ADIPOQ and PPARG on antipsychotic-induced weight gain, our comprehensive examination of these two genes contributes to understanding the biology of this serious side effect. More research on glucose metabolism genes is warranted to elucidate their role in metabolic changes during antipsychotic treatment.
authors: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada; Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
authors: Eva J
authors: EJ
authors: Brandl
authors: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada.
authors: Arun K
authors: AK
authors: Tiwari
authors: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: Clement C
authors: CC
authors: Zai
authors: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: Nabilah I
authors: NI
authors: Chowdhury
authors: Department of Psychiatry, College of Physicians and Surgeons, Columbia University and the New York State Psychiatric Institute, New York City, NY, USA.
authors: Jeffrey A
authors: JA
authors: Lieberman
authors: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors: Herbert Y
authors: HY
authors: Meltzer
authors: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors: James L
authors: JL
authors: Kennedy
authors: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: daniel.mueller@camh.ca.
authors: Daniel J
authors: DJ
authors: Müller
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D050177:Overweight / Q000139:chemically induced* / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000188:drug therapy / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D052242:Adiponectin; D014150:Antipsychotic Agents; D047495:PPAR gamma; D001569:Benzodiazepines; D003024:Clozapine; D000077152:Olanzapine
keywords: Clozapine; Glucose-related genes; Haplotypes; Olanzapine; Pharmacogenetics; Polymorphisms