No abnormality in the gene for the G protein stimulatory alpha subunit in patients with bipolar disorder.
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.
Ram
A
A
Clinical Neurogenetics Branch, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md, USA.
Guedj
F
F
Cravchik
A
A
Weinstein
L
L
Cao
Q
Q
Badner
J A
JA
Goldin
L R
LR
Grisaru
N
N
Manji
H K
HK
Belmaker
R H
RH
Gershon
E S
ES
Gejman
P V
PV
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
D019205:GTP-Binding Protein alpha Subunits, Gs