双相情感障碍与编码 18 kDa 转位蛋白（TSPO）的基因中的 rs6971 多态性有关。
Bipolar Disorder is associated with the rs6971 polymorphism in the gene encoding 18 kDa Translocator Protein (TSPO).
机构信息
Division of Brain Sciences, Imperial College, London, United Kingdom; Imanova Centre for Imaging Sciences, Hammersmith Hospital Campus, London, United Kingdom.
出版信息
Psychoneuroendocrinology. 2013 Nov;38(11):2826-9. doi: 10.1016/j.psyneuen.2013.07.007. Epub 2013 Aug 12.
Abstract
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.
摘要
TSPO 介导的胆固醇向线粒体的转运是类固醇合成的必要步骤。TSPO 基因中的 rs6971 多态性导致跨膜结构域内的氨基酸取代（Ala147Thr），胆固醇结合口袋就位于此处，并且已被证明会影响甾体生成途径。我们报告了 TSPO 多态性与英国惠康信托基金会病例对照联盟全基因组数据集以及精神病基因组联盟双相情感障碍组之间的双相情感障碍诊断之间的名义关联（OR=1.11，p=0.007；OR=1.10，p=0.011，分别）。我们提出，这种氨基酸取代会影响下丘脑-垂体-肾上腺（HPA）的调节，从而可能导致双相情感障碍。这支持了 HPA 失调在双相情感障碍中起因果作用的假说，而不仅仅是疾病的结果。
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