No abnormality in the gene for the G protein stimulatory α subunit in patients with bipolar disorder

Anca Ram, Françoise Guedj, Anibal Cravchik, Lee Weinstein, Qiuhe Cao, Judith A. Badner, Lynn R. Goldin, Nimrod Grisaru, Husseini K. Manji, Robert H. Belmaker, Elliot S. Gershon, Pablo V. Gejman

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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 G(s)-α) in peripheral leukocytes and in postmortem tissues of patients with bipolar disorder. Methods: The hypothesis that a mutation in G(s)-α gene confers an increased susceptibility to bipolar disorder was tested by the following strategies: (1) mutational screening of the G(s)-a 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. Results: No structural or regulatory mutations in this gene were found in bipolar disorder; the results of association and genetic linkage were negative. Conclusion: Our results do not support the speculation that the G(s)-α protein gene has a role in the genetic predisposition to bipolar disorder.

Original languageEnglish
Pages (from-to)44-48
Number of pages5
JournalArchives of General Psychiatry
Volume54
Issue number1
DOIs
StatePublished - 1 Jan 1997

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