title: Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain.
abstract: BACKGROUND
  Antipsychotic-induced weight gain (AIWG) is a serious side-effect of antipsychotic medication leading to metabolic syndrome and increased cardiovascular morbidity. Unfortunately, there are still no valid predictors to assess an individual's risk to gain weight. Previous studies have indicated an impact of genetic variation in the genes encoding leptin, LEP, and leptin receptor, LEPR, on AIWG, but results have not been conclusive. Thus, we investigated polymorphisms in both genes for an association with AIWG.
  
  
  METHODS
  A total of 181 schizophrenic and schizoaffective patients treated with various antipsychotics were included. In a small subset of patients, leptin plasma levels were additionally obtained. Five polymorphisms in LEP and LEPR (LEP: rs7799039 (-2548G/A polymorphism), rs10954173, rs3828942; LEPR: rs1327120, rs1137101 (Q223R polymorphism) were genotyped using TaqMan assays. Statistical association with % weight change from baseline weight was performed using ANCOVA with baseline weight as covariate.
  
  
  RESULTS
  ANCOVA showed a non-significant trend for genotype association of the rs7799039 marker (p=.068). No significant association of the other LEP and LEPR SNPs with AIWG was detected. However, we found a significant association between a haplotype of LEP rs7799039G-rs10954173G-rs3828942G (p=.035) and AIWG. The rs7799039 G-allele (p=.042) and G-allele of rs3828942 (p=.032) were associated with higher weight gain.
  
  
  CONCLUSIONS
  Our study supports the hypothesis of an impact of LEP gene variation on AIWG. Limitations of our study include heterogeneous samples, short treatment duration and multiple comparisons. Our findings were compared to previous studies in detail in order to provide the readers with a more conclusive picture. However, further studies are warranted including more gene variants and interaction analyses with other genes of the leptin-melanocortin pathway.
authors.affiliation: Centre of Addiction and Mental Health, Neurogenetics Section, Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: E J
authors.initials: EJ
authors.lastname: Brandl
authors.forename: C
authors.initials: C
authors.lastname: Frydrychowicz
authors.forename: A K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: T A P
authors.initials: TA
authors.lastname: Lett
authors.forename: W
authors.initials: W
authors.lastname: Kitzrow
authors.forename: S
authors.initials: S
authors.lastname: Büttner
authors.forename: S
authors.initials: S
authors.lastname: Ehrlich
authors.forename: H Y
authors.initials: HY
authors.lastname: Meltzer
authors.forename: J A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: D J
authors.initials: DJ
authors.lastname: Müller
authors.forename: I
authors.initials: I
authors.lastname: Puls
mesh_terms: D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects*; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020738:Leptin / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D054411:Receptors, Leptin / Q000235:genetics*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
chemical_list: D014150:Antipsychotic Agents; D020738:Leptin; D054411:Receptors, Leptin