双相情感障碍患者中G蛋白刺激性α亚基基因无异常。

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

作者信息

Ram A, Guedj F, Cravchik A, Weinstein L, Cao Q, Badner J A, Goldin L R, Grisaru N, Manji H K, Belmaker R H, Gershon E S, Gejman P V

机构信息

Clinical Neurogenetics Branch, National Institute of Mental Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Md, USA.

出版信息

Arch Gen Psychiatry. 1997 Jan;54(1):44-8. doi: 10.1001/archpsyc.1997.01830130048010.

DOI:10.1001/archpsyc.1997.01830130048010

PMID:9006399

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.

CONCLUSION

Our results do not support the speculation that the Gs-alpha protein gene has a role in the genetic predisposition to bipolar disorder.

摘要

背景

关于异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）参与双相情感障碍的现有证据主要基于锂盐对G蛋白功能的影响以及双相情感障碍患者外周血白细胞和死后组织中G蛋白（最显著的是Gs-α）浓度或功能的改变。

方法

通过以下策略检验Gs-α基因突变会增加患双相情感障碍易感性的假设：（1）采用变性梯度凝胶电泳对无亲缘关系的双相情感障碍患者的Gs-α亚基基因编码序列和启动子序列进行突变筛查；（2）利用来自至少有1名患病儿童的美国家庭的遗传等位基因信息，对一个常见的沉默外显子多态性进行关联分析和连锁分析。关联分析采用连锁不平衡传递检验；连锁分析采用非参数方法。