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载脂蛋白基因()中的 rs6971 变异与攻击性和冲动性相关,但与青年人群代表性样本中的焦虑无关。

Variation rs6971 in the Translocator Protein Gene () is Associated with Aggressiveness and Impulsivity but Not with Anxiety in a Population-Representative Sample of Young Adults.

机构信息

Institute of Psychology, University of Tartu, Tartu, Estonia.

Institute of Genomics, University of Tartu, Tartu, Estonia.

出版信息

J Genet Psychol. 2021 Mar-May;182(3):149-162. doi: 10.1080/00221325.2021.1896470. Epub 2021 Mar 26.

Abstract

Expression of the 18-kDa translocator protein (TSPO), originally identified as a peripheral benzodiazepine receptor, has been found to be altered in several psychiatric disorders. A common single nucleotide polymorphism (rs6971) in the TSPO gene leads to an amino acid substitution, Ala147Thr, which dramatically alters the affinity with which TSPO binds drug ligands. As cholesterol also binds TSPO in the same transmembrane domain, it is suggested that this substitution may impair the ability of TSPO to bind or import cholesterol, and hence may affect steroid synthesis and hypothalamic-pituitary-adrenal function. The analysis was carried out on older birth cohort (n = 655) of the longitudinal Estonian Children Personality, Behavior and Health Study sample. Anxiety, aggressive behavior, impulsiveness, and history of stressful life events were self-reported in various data collection waves. Psychiatric assessment of lifetime prevalence of anxiety disorders was carried out at 25 years of age by experienced clinical psychologists. rs6971 was genotyped in all participants. rs6971 was not associated with self-reported levels of anxiety or lifetime prevalence of anxiety disorders. However, participants homozygous for the minor A allele displayed the highest aggressiveness and dysfunctional impulsivity scores. The positive, adaptive aspect of impulsivity was sensitive to stressful life events, as the AA genotype was associated with functional impulsivity only when the participants had experienced a low number of stressful life events during childhood. rs6971 polymorphism may be related to development of aggressiveness and impulsivity by adulthood, regardless of the participants' gender.

摘要

18kDa 转位蛋白(TSPO)的表达最初被鉴定为外周苯二氮䓬受体,在几种精神疾病中发现其发生改变。TSPO 基因中的一个常见单核苷酸多态性(rs6971)导致氨基酸取代,即 Ala147Thr,这极大地改变了 TSPO 与药物配体结合的亲和力。由于胆固醇也在 TSPO 的同一跨膜结构域结合,因此有人认为这种取代可能会损害 TSPO 结合或摄取胆固醇的能力,从而可能影响类固醇合成和下丘脑-垂体-肾上腺功能。该分析是在纵向爱沙尼亚儿童个性、行为和健康研究样本的较年长出生队列(n=655)中进行的。在不同的数据收集波中,焦虑、攻击行为、冲动和生活压力事件史均由自身报告。在 25 岁时,由经验丰富的临床心理学家对终生焦虑障碍的患病率进行了精神病学评估。所有参与者均进行了 rs6971 基因分型。rs6971 与自身报告的焦虑水平或终生焦虑障碍患病率无关。然而,纯合子 AA 基因型的参与者表现出最高的攻击性和功能失调的冲动性评分。冲动的积极、适应性方面对生活压力事件敏感,因为只有当参与者在儿童时期经历了较少的生活压力事件时,AA 基因型才与功能性冲动有关。rs6971 多态性可能与成年后的攻击性和冲动性发展有关,而与参与者的性别无关。

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