title: Impact of histamine receptors H1 and H3 polymorphisms on antipsychotic-induced weight gain.
abstract: A positive correlation between antipsychotic-induced weight gain (AIWG) and the antagonist effect of antipsychotic drugs at the histamine H1 receptor (HRH1) as well as the agonist effect at the histamine H3 receptor (HRH3) in the brain has been consistently demonstrated. We investigated the potential impact of single-nucleotide polymorphisms (SNPs) in HRH1 and HRH3 genes on AIWG.
  
  
  
  We analysed 40 tagSNPs in HRH1 (n = 34) and HRH3 (n = 6) in schizophrenia/schizoaffective disorder patients (n = 193) primarily treated with clozapine or olanzapine for up to 14 weeks. Linear regression was used to evaluate the association between SNPs and AIWG, with baseline weight and treatment duration as covariates.
  
  
  
  In HRH1, a nominal association of rs7639145 with AIWG was observed in patients of European ancestry treated with either clozapine or olanzapine (P= 0.043; β = 1.658; n = 77). We observed nominal association for two HRH1 SNPs rs346074 (P = 0.002; β = -5.024) and rs13064530 (P= 0.004; β = -5.158) in patients of African ancestry treated with either clozapine or olanzapine (n = 37). However, the above associations are not significant after correcting for multiple testing. In HRH3, we did not observe association in either ancestry.
  
  
  
  The current study suggests that SNPs in HRH1 and HRH3 may not have a major role in AIWG.
authors.affiliation: a Neurogenetics Section, Neuroscience Department , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada.|b Department of Psychiatry , University of Toronto , Toronto , ON , Canada.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: a Neurogenetics Section, Neuroscience Department , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada.
authors.forename: Danning
authors.initials: D
authors.lastname: Zhang
authors.affiliation: a Neurogenetics Section, Neuroscience Department , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada.|b Department of Psychiatry , University of Toronto , Toronto , ON , Canada.
authors.forename: Jennie G
authors.initials: JG
authors.lastname: Pouget
authors.affiliation: a Neurogenetics Section, Neuroscience Department , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada.|b Department of Psychiatry , University of Toronto , Toronto , ON , Canada.
authors.forename: Clement C
authors.initials: CC
authors.lastname: Zai
authors.affiliation: a 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.affiliation: a Neurogenetics Section, Neuroscience Department , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada.|c Department of Psychiatry and Psychotherapy , Campus Mitte, Charité Universitätsmedizin Berlin , Berlin , Germany.
authors.forename: Eva J
authors.initials: EJ
authors.lastname: Brandl
authors.affiliation: a Neurogenetics Section, Neuroscience Department , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.affiliation: a Neurogenetics Section, Neuroscience Department , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada.
authors.forename: Natalie
authors.initials: N
authors.lastname: Freeman
authors.affiliation: d Department of Psychiatry, College of Physicians and Surgeons , Columbia University and the New York State Psychiatric Institute , New York City , NY , USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.affiliation: e Northwestern University Feinberg School of Medicine , Chicago , IL , USA.
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.affiliation: a Neurogenetics Section, Neuroscience Department , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada.|b Department of Psychiatry , University of Toronto , Toronto , ON , Canada.
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.affiliation: a Neurogenetics Section, Neuroscience Department , Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health , Toronto , ON , Canada.|b Department of Psychiatry , University of Toronto , Toronto , ON , Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D000077152:Olanzapine / Q000009:adverse effects; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000188:drug therapy*; D011969:Receptors, Histamine H1 / Q000235:genetics*; D018100:Receptors, Histamine H3 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy*; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D011969:Receptors, Histamine H1; D018100:Receptors, Histamine H3; D003024:Clozapine; D000077152:Olanzapine
keywords: SNP; Schizophrenia; clozapine; histamine receptor; weight gain