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No Abnormality in the Gene for the G Protein Stimulatory Subunit in Patients With Bipolar Disorder
Anca Ram, MD;
Françoise Guedj, MD;
Anibal Cravchik, MD, PhD;
Lee Weinstein, MD;
Qiuhe Cao, MD;
Judith A. Badner, MD, PhD;
Lynn R. Goldin, PhD;
Nimrod Grisaru, MD;
Husseini K. Manji, MD;
Robert H. Belmaker, MD;
Elliot S. Gershon, MD;
Pablo V. Gejman, MD
Arch Gen Psychiatry. 1997;54(1):44-48.
Abstract
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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- ) in peripheral leukocytes and in postmortem tissues of patients with bipolar disorder.
Methods The hypothesis that a mutation in Gs- gene confers an increased susceptibility to bipolar disorder was tested by the following strategies: (1) mutational screening of the Gs- 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 Gs- protein gene has a role in the genetic predisposition to bipolar disorder.
Author Affiliations
From the Clinical Neurogenetics Branch (Drs Ram, Guedj, Cravchik, Cao, Badner, Goldin, Gershon, and Gejman) and the Experimental Therapeutics Branch (Dr Manji), National Institute of Mental Health, and the Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (Dr Weinstein), Bethesda, Md; and the Beer Sheva Mental Health Center, Ben Gurion University (Drs Grisaru and Belmaker), Beer Sheva, Israel.
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