title: Investigation of melanocortin system gene variants in antipsychotic-induced weight gain.
abstract: OBJECTIVE
  The use of second-generation antipsychotic medications may result in substantial weight gain in a subset of schizophrenia patients. Distinct populations of neurons expressed in the hypothalamus, including the cocaine- and amphetamine-regulated transcript (CART), the polypeptide pro-opiomelanocortin (POMC) and the agouti-related protein (AGRP), have regulatory roles in weight control and energy homeostasis. Thus, we investigated the potential role of CART, POMC and AGRP genetic variants in antipsychotic-induced weight gain (AIWG).
  
  
  METHODS
  Five CART single nucleotide polymorphisms (SNPs) (rs10515115, rs3763153, rs3857384, rs11575893, rs16871471), three POMC SNPs (rs6713532, rs1047521, rs3754860) and one AGRP SNP (rs1338993), were genotyped in 218 patients treated with antipsychotics for chronic schizophrenia and evaluated for AIWG. We compared weight change (%) across genotypic groups using analysis of covariance.
  
  
  RESULTS
  None of the SNPs in POMC, CART, AGRP were significantly associated with AIWG in the refined samples stratified by ethnicity and medication treatment.
  
  
  CONCLUSIONS
  In this exploratory study, we observed that POMC, CART and AGRP gene variants are not a major contributor to AIWG. However larger samples are required to completely rule out their effect on AIWG.
authors.affiliation: Neurogenetics Section, Neuroscience Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto, ON , Canada.
authors.forename: Nabilah I
authors.initials: NI
authors.lastname: Chowdhury
authors.forename: Renan P
authors.initials: RP
authors.lastname: Souza
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Eva J
authors.initials: EJ
authors.lastname: Brandl
authors.forename: Michelle
authors.initials: M
authors.lastname: Sicard
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000328:Adult; D054369:Agouti-Related Protein / Q000235:genetics*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy*; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics*; D055815:Young Adult; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; D014150:Antipsychotic Agents; D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D011333:Pro-Opiomelanocortin