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-α) in peripheral leukocytes and in postmortem tissues of patients with bipolar disorder.
The hypothesis that a mutation in Gs-α gene confers an increased susceptibility to bipolar disorder was tested by the following strategies: (1) mutational screening of the Gs-α 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, non-parametric methods were used.
No structural or regulatory mutations in this gene were found in bipolar disorder; the results of association and genetic linkage were negative.
Our results do not support the speculation that the Gs-α protein gene has a role in the genetic predisposition to bipolar disorder.
Ram A, Guedj F, Cravchik A, Weinstein L, Cao Q, Badner JA, Goldin LR, Grisaru N, Manji HK, Belmaker RH, Gershon ES, Gejman PV. No Abnormality in the Gene for the G Protein Stimulatory α Subunit in Patients With Bipolar Disorder. Arch Gen Psychiatry. 1997;54(1):44-48. doi:10.1001/archpsyc.1997.01830130048010