KIBRA, MTNR1B, and FKBP5 genotypes are associated with decreased odds of incident delirium in elderly post-surgical patients

Abstract

Despite the association between cognitive impairment and delirium, little is known about whether genetic differences that confer cognitive resilience also confer resistance to delirium. To investigate whether older adults without postoperative delirium, compared with those with postoperative delirium, are more likely to have specific single nucleotide polymorphisms (SNPs) in the FKBP5, KIBRA, KLOTHO, MTNR1B, and SIRT1 genes known to be associated with cognition or delirium. This prospective nested matched exploratory case–control study included 94 older adults who underwent orthopedic surgery and screened for postoperative delirium. Forty-seven subjects had incident delirium, and 47 age-matched controls were not delirious. The primary study outcome was genotype frequency for the five SNPs. Compared with participants with delirium, those without delirium had higher adjusted odds of KIBRA SNP rs17070145 CT/TT [vs. CC; adjusted odds ratio (aOR) 2.80, 95% confidence interval (CI) 1.03, 7.54; p = 0.04] and MTNR1B SNP rs10830963 CG/GG (vs. CC; aOR 4.14, 95% CI 1.36, 12.59; p = 0.01). FKBP5 SNP rs1360780 CT/TT (vs. CC) demonstrated borderline increased adjusted odds of not developing delirium (aOR 2.51, 95% CI 1.00, 7.34; p = 0.05). Our results highlight the relevance of KIBRA, MTNR1B, and FKBP5 in understanding the complex relationship between delirium, cognition, and sleep, which warrant further study in larger, more diverse populations.

A Molecular Framework for Delirium

“…One metaanalysis did not find an association between Melatonin Receptor-1B (MTNR1B) and delirium, 36 although studies published since then have provided more data in support of an association. 39 Melatonin signaling is particularly interesting given the strong link between circadian disruption and delirium. 11,12 The Influence of Environment on Delirium Clinical interventions that address common delirium precipitants have a dramatic influence on the incidence of delirium in hospitalized patients.…”

“…One meta-analysis did not find an association between Melatonin Receptor-1B (MTNR1B) and delirium, 36 although studies published since then have provided more data in support of an association. 39 Melatonin signaling is particularly interesting given the strong link between circadian disruption and delirium. 11,12…”

A novel approach GRNTSTE to reconstruct gene regulatory interactions applied to a case study for rat pineal rhythm gene

“…Mechanistically, the motif stringency of XBP1s promoter binding sites dictates XBP1s's ability to drive 12-h rhythms of nascent mRNA transcription at dawn and dusk. Terrelonge et al 64 KIBRA, MTNR1B, and FKBP5 play an important roles in the complex relationship between delirium, cognition, and sleep, and warrant further study in larger, more diverse populations. Secretion of the stress hormone cortisol follows a circadian rhythm and is stimulated following stress exposure.…”

Association of job stress, FK506 binding protein 51 (FKBP5) gene polymorphisms and their interaction with sleep disturbance

“…FKBP5 single nucleotide polymorphisms (SNPs) ( i.e., rs3800373 and rs1360780 ) may increase suicide risk in individuals with a history of childhood trauma ( Roy et al, 2010 ; Womersley et al, 2022 ). As many studies have reported, FKBP5 variants have been linked to neuropsychiatric conditions, including depression, anxiety, posttraumatic stress disorder and cognitive impairment, all of which share some symptoms with sleep disturbance ( Wang, Shelton & Dwivedi, 2018 ; Hernández-Díaz et al, 2019 ; Terrelonge et al, 2022 ). In addition, a study reported a potential association between the FKBP5 rs9470080 variant and subjective health complaints, in which the FKBP5 rs9470080 CC genotype was associated with poor sleep quality complaints in the female working population ( Sannes et al, 2020 ).…”