DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice
DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice
复制标题
DOI：
10.1111/appy.12009
复制
发表时间：
2013-03-01
影响因子：
3.5
通讯作者：
Sasak, Tsukasa
中科院分区：
文献类型：
--
作者：
Kawamura, Yoshiya;Takahashi, Taiki;Sasak, Tsukasa
简介 跨期选择中的冲动性已被操作为延迟贴现，指的是对更快、更小的奖励的偏好。 FK506 结合蛋白 5 (FKBP5) 是糖皮质激素受体 (GR) 的共伴侣。 FKBP5 过度表达会导致 GR 抵抗，导致血浆皮质醇水平升高。高皮质醇水平与跨期选择的低冲动性相关。本研究的目的是探讨 FKBP5 中的单核苷酸多态性 (SNP) 对延迟贴现的影响。方法 参与者包括 91 名健康日本人（66 名男性和 25 名女性，平均年龄为 40.9 +/- 6.9 岁）。每个参与者都完成了柯比的货币选择问卷（MCQ）并捐赠了全血样本。使用 DigiTag2 对 FKBP5 中的 5 个 SNP 进行基因分型。对双曲时间贴现率 (k) 进行了 100,000 次排列的 SNP 线性回归分析。结果 两个 SNP 因其次要等位基因频率较低而被排除在分析之外。 SNP rs1360780 显示出显着的关联；具有更多次要等位基因 (T) 的参与者在延迟增益的跨期选择中较少冲动（多重校正 P=0.047）。讨论 重要的 SNP rs1360780 位于与激素反应元件 (HRE) 结合序列相邻的区域，其中转录因子结合并改变 FKBP5 的转录。 rs1360780 的小等位基因 (T) 会导致 FKBP5 过度表达，可能会通过 GR 抵抗和随后的高皮质醇水平来减少跨期选择的冲动（即延迟贴现）。这是第一项证明 FKBP5 与跨期选择冲动之间存在关联的研究。
Introduction Impulsivity in intertemporal choice has been operationalized as delay discounting, referring to the preference for a sooner, smaller reward. FK506 binding protein 5 (FKBP5) is a co-chaperone of the glucocorticoid receptor (GR). FKBP5 overexpression causes GR resistance, resulting in increased plasma cortisol levels. High cortisol levels are associated with low impulsivity in intertemporal choice. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) in FKBP5 on delay discounting. Methods The participants consisted of 91 healthy Japanese people (66 males and 25 females with a mean age of 40.9 +/- 6.9 years). Each participant completed Kirby's monetary choice questionnaire (MCQ) and donated a whole blood sample. Five SNPs in FKBP5 were genotyped using the DigiTag2. SNP linear regression analyses with 100,000 permutations were conducted for the hyperbolic time-discount rate (k). Results Two SNPs were excluded from analysis because of their low minor allelic frequencies. The SNP rs1360780 showed a significant association; participants with more minor alleles (T) were less impulsive in intertemporal choice for delayed gain (multiplicity-corrected P=0.047). Discussion The significant SNP rs1360780 is located in the region adjacent to the hormone response element (HRE)-binding sequence where transcription factors bind and alter the transcription of FKBP5. A minor allele (T) of rs1360780, which causes FKBP5 overexpression, may reduce impulsivity in intertemporal choice (i.e. delay discounting) via GR resistance and the subsequent high cortisol levels. This is the first study to demonstrate an association between FKBP5 and impulsivity in intertemporal choice.