title: No abnormality in the gene for the G protein stimulatory alpha subunit in patients with bipolar disorder.
abstract: BACKGROUND
  The available evidence for an involvement of the heterotrimeric guanine-nucleotide-binding proteins (G proteins) in bipolar disorder relies primarily on the effects of lithium salts on G protein function and on alterations in the concentration or function of G proteins (most notably Gs-alpha) in peripheral leukocytes and in postmortem tissues of patients with bipolar disorder.
  
  
  METHODS
  The hypothesis that a mutation in Gs-alpha gene confers an increased susceptibility to bipolar disorder was tested by the following strategies: (1) mutational screening of the Gs-alpha subunit gene coding sequences and promoter sequences by denaturing gradient gel electrophoresis in unrelated individuals with bipolar disorder and (2) association and linkage analyses with a common silent exonic polymorphism, using genetic allelic information from American families with at least 1 affected child. For association analysis, the transmission test for linkage disequilibrium was used; for linkage analysis, nonparametric methods were used.
  
  
  RESULTS
  No structural or regulatory mutations in this gene were found in bipolar disorder; the results of association and genetic linkage were negative.
  
  
  CONCLUSIONS
  Our results do not support the speculation that the Gs-alpha protein gene has a role in the genetic predisposition to bipolar disorder.
authors.affiliation: Clinical Neurogenetics Branch, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ram
authors.forename: F
authors.initials: F
authors.lastname: Guedj
authors.forename: A
authors.initials: A
authors.lastname: Cravchik
authors.forename: L
authors.initials: L
authors.lastname: Weinstein
authors.forename: Q
authors.initials: Q
authors.lastname: Cao
authors.forename: J A
authors.initials: JA
authors.lastname: Badner
authors.forename: L R
authors.initials: LR
authors.lastname: Goldin
authors.forename: N
authors.initials: N
authors.lastname: Grisaru
authors.forename: H K
authors.initials: HK
authors.lastname: Manji
authors.forename: R H
authors.initials: RH
authors.lastname: Belmaker
authors.forename: E S
authors.initials: ES
authors.lastname: Gershon
authors.forename: P V
authors.initials: PV
authors.lastname: Gejman
mesh_terms: D001483:Base Sequence; D001714:Bipolar Disorder / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000235:genetics; D012307:Risk Factors
chemical_list: D019205:GTP-Binding Protein alpha Subunits, Gs