DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice

Abstract

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 Ϯ 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.

Genetic influences on delay discounting in smokers: examination of a priori candidates and exploration of dopamine-related haplotypes

“…The association between the T allele of rs1800497 and discounting is consistent with one previous study (Eisenberg et al 2007), while two other studies did not find this association (Kawamura et al 2013; Gray and MacKillop 2014). Again, considerable methodological heterogeneity is present within these studies, which may contribute to these mixed findings.…”

Common variants in FKBP5 gene and major depressive disorder (MDD) susceptibility: a comprehensive meta-analysis

“…There is evidence to suggest that rs1360780 TT homozygous carriers have higher FKBP5 levels, and these are twice as high as those with C+ genotypes ( P  = 0.024)15. These different expression patterns of FKBP5 might be due to different transcriptional activity of FKBP5, which is regulated by a conserved HRE located less than 200 bp away from rs1360780 in intron 231. This FKBP5 variant has also been associated with hippocampal volume, an endophenotype of MDD17.…”

Variation in the <i>DRD2</i> gene affects impulsivity in intertemporal choice

“…In the current study, the Japanese version of the MCQ for delayed gain used the same procedure as previous studies [19,[44][45][46][47] for assessing time-discount rates. As in our previous studies, One dollar was converted to 100 yen (e.g.…”

“…"Would you prefer 2700 yen now or 5000 yen in three weeks?") [45][46][47]. Three time-discount ratessmall, medium, and large gains, and represented by k (S), k (M), and k (L), respectively-were obtained for each participant.…”