title: The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain.
abstract: OBJECTIVE
  Antipsychotics with high weight gain-inducing propensities influence the expression of immune and neurotrophin genes, which have been independently related to obesity indices. Thus, we investigated whether variants in the genes encoding interleukin (IL)-1β, IL-2, and IL-6 and brain-derived neurotrophic factor (BDNF) Val66Met are associated with antipsychotic-induced weight gain (AIWG).
  
  
  METHODS
  Nineteen polymorphisms were genotyped using Taqman(®) assays in 188 schizophrenia patients on antipsychotic treatment for up to 14 weeks. Mean weight change (%) from baseline was compared across genotypic groups using analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality Reduction.
  
  
  RESULTS
  In European patients, IL-1β rs16944*GA (P = 0.013, Pcorrected = 0.182), IL-1β rs1143634*G (P = 0.001, Pcorrected = 0.014), and BDNF Val66Met (Val/Val, P = 0.004, Pcorrected = 0.056) were associated with greater AIWG, as were IL-1β rs4849127*A (P = 0.049, Pcorrected = 0.784), and IL-1β rs16944*GA (P = 0.012, Pcorrected = 0.192) in African Americans. BDNF Val66Met interacted with both IL-1β rs13032029 (Val/Met+ TT, PPerm = 0.029), and IL-6 rs2069837 (Val/Val+ AA, PPerm = 0.021) in Europeans, in addition to IL-1β rs16944 (Val/Val+ GA, PPerm = 0.006) in African Americans.
  
  
  CONCLUSIONS
  SNPs across IL-1β and BDNF Val66Met may influence AIWG. Replication of these findings in larger, independent samples is warranted.
authors.affiliation: Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health & Department of Psychiatry, University of Toronto , Toronto, ON , Canada.
authors.forename: Trehani M
authors.initials: TM
authors.lastname: Fonseka
authors.forename: Arun K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Vanessa F
authors.initials: VF
authors.lastname: Gonçalves
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Goldstein
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Sidney H
authors.initials: SH
authors.lastname: Kennedy
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D014633:Valine / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; C508585:IL1B protein, human; C508594:IL2 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; C579455:BDNF protein, human; D008715:Methionine; D014633:Valine
keywords: BDNF; IL-1 β; antipsychotic-induced weight gain; cytokine; genetics