Bipolar Disorder is associated with the rs6971 polymorphism in the gene encoding 18 kDa Translocator Protein (TSPO)

详细信息    查看全文

• 作者：Aless ; ro Colasanti ; David R. Owen ; Detelina Grozeva ; Eugenii A. Rabiner ; Paul M. Matthews ; Nick Craddock ; Allan H. Young
• 关键词：Translocator Protein ; Cortisol ; HPA ; Neurosteroids ; rs6971 ; Genome-wide ; WTCCC ; Polymorphism ; Mitochondria ; Bipolar Disorder
• 刊名：Psychoneuroendocrinology
• 出版年：November, 2013
• 年：2013
• 卷：38
• 期：11
• 页码：2826-2829
• 全文大小：336 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

TSPO mediated transport of cholesterol into the mitochondrion is a necessary step in steroid synthesis. The rs6971 polymorphism in the TSPO gene causes an amino acid substitution (Ala147Thr) within the transmembrane domain where the cholesterol-binding pocket is located, and has been shown to affect the steroidogenic pathway. We report a nominal association between this TSPO polymorphism and the diagnosis of Bipolar Disorder in both the genome-wide dataset of the Wellcome Trust Case-Control Consortium and the Psychiatric Genome-Wide Association Study Consortium Bipolar Disorder group (OR = 1.11, p = 0.007; OR = 1.10, p = 0.011, respectively). We propose that the amino acid substitution affects hypothalamic-pituitary-adrenal (HPA) regulation, and hence may predispose to Bipolar Disorder. This supports the hypothesis that HPA dysregulation has a causal role in Bipolar Disorder, and is not just a consequence of the disease.