Department of Human Morphology and Applied Biology, University of Pisa, via Volta, 4-56126 Pisa, Italy.
Curr Mol Med. 2012 May;12(4):483-7.
A role for the protein that mediates the rate-limiting step of steroidogenesis, the 18 kDa Translocator Protein (TSPO), has been suggested in the pathophysiology of Adult Separation Anxiety Disorder (ASAD). It has been shown that ASAD patients have 1) low TSPO expression levels and 2) a high frequency of the allele that substitutes Ala with Thr at position 147 of TSPO. The Thr147 ASAD-associated allele has been recently related with a low pregnenolone production. The aim of the present work was to evaluate the relationship between TSPO expression levels and Ala147Thr single nucleotide polymorphism (SNP), which are the two TSPO biological parameters that we have previously examined separately. A further aim was to confirm the genetic association of Ala147Thr SNP with ASAD in an extended case-control sample and to investigate whether this SNP was related to an anxious attachment style that is thought to be connected to ASAD.
TSPO expression levels were compared among patients with ASAD (n=26), without ASAD (n=26) and control samples (n=10) stratified into the two genotype groups: those with the Ala147 genotype (named "normal pregnenolone production") and those with the Thr147 genotype (named "reduced pregnenolone production"). The case-control genetic study included patients with (n=87) or without (n=101) ASAD and 236 controls. In the patient group, the association between the Ala147Thr SNP and an anxious attachment style was analysed by stepwise logistic regression analysis.
The genotype with the lowest TSPO expression levels was the "normal pregnenolone production" genotype in the ASAD group. The genetic Ala147Thr SNP confirmed an excess of the Thr147 allele in ASAD patients. Stepwise logistic regression analysis did not show an association with an anxious attachment style.
ASAD individuals who expressed normal TSPO levels exhibited the "reduced pregnenolone production" genotype. In contrast, the ASAD individuals with the "normal pregnenolone production" genotype expressed low TSPO levels. It is possible that low TSPO expression levels could compromise normal pregnenolone production. Such evidence may have therapeutic implications because it has been documented that drugs targeting TSPO increased pregnenolone production and have anxiolytic effects.
介导类固醇生成限速步骤的蛋白质——18kDa 转位蛋白（TSPO），在成人分离焦虑症（ASAD）的病理生理学中发挥作用。已经表明，ASAD 患者 1）TSPO 表达水平低，2）TSPO 第 147 位的 Ala 被 Thr 取代的等位基因频率高。最近，ASAD 相关的 Thr147 等位基因与孕酮生成减少有关。本研究旨在评估 TSPO 表达水平与 Ala147Thr 单核苷酸多态性（SNP）之间的关系，这是我们之前分别检查的两个 TSPO 生物学参数。进一步的目的是在扩展的病例对照样本中证实 Ala147Thr SNP 与 ASAD 的遗传关联，并研究该 SNP 是否与被认为与 ASAD 相关的焦虑依恋风格有关。
比较 ASAD 患者（n=26）、无 ASAD 患者（n=26）和对照组（n=10）之间的 TSPO 表达水平，对照组分为两种基因型组：Ala147 基因型（命名为“正常孕烯醇酮生成”）和 Thr147 基因型（命名为“降低孕烯醇酮生成”）。病例对照遗传研究包括患有（n=87）或不患有（n=101）ASAD 的患者和 236 名对照。在患者组中，通过逐步逻辑回归分析分析 Ala147Thr SNP 与焦虑依恋风格的关系。
ASAD 组中表达最低 TSPO 水平的基因型是“正常孕烯醇酮生成”基因型。遗传 Ala147Thr SNP 证实 ASAD 患者中 Thr147 等位基因过多。逐步逻辑回归分析未显示与焦虑依恋风格相关。
表达正常 TSPO 水平的 ASAD 个体表现出“降低的孕烯醇酮生成”基因型。相比之下，具有“正常孕烯醇酮生成”基因型的 ASAD 个体的 TSPO 水平较低。低 TSPO 表达水平可能会影响正常孕烯醇酮的生成。这种证据可能具有治疗意义，因为已经证明靶向 TSPO 的药物增加了孕烯醇酮的生成并具有抗焦虑作用。
