Department of Neurology, School of Medicine, University of California, San Francisco, CA, USA.
Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Sci Rep. 2022 Jan 11;12(1):556. doi: 10.1038/s41598-021-04416-z.
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.
尽管认知障碍与谵妄之间存在关联，但对于赋予认知弹性的遗传差异是否也赋予对谵妄的抵抗力知之甚少。为了研究与认知或谵妄相关的 FKBP5、KIBRA、KLOTHO、MTNR1B 和 SIRT1 基因中是否存在特定的单核苷酸多态性（SNP），这些 SNP 使接受过手术后没有发生谵妄的老年人与发生了术后谵妄的老年人相比，更有可能存在这些 SNP。这项前瞻性嵌套匹配的探索性病例对照研究纳入了 94 名接受骨科手术并筛查术后谵妄的老年人。47 名患者发生了谵妄，47 名年龄匹配的对照者没有发生谵妄。主要研究结局是五个 SNP 的基因型频率。与发生谵妄的参与者相比，未发生谵妄的参与者 KIBRA SNP rs17070145 CT/TT（与 CC 相比；调整后的优势比[aOR] 2.80，95%置信区间[CI] 1.03-7.54；p=0.04）和 MTNR1B SNP rs10830963 CG/GG（与 CC 相比；aOR 4.14，95%CI 1.36-12.59；p=0.01）的调整后比值优势更高。FKBP5 SNP rs1360780 CT/TT（与 CC 相比）表现出发生谵妄的调整后比值优势略有增加（aOR 2.51，95%CI 1.00-7.34；p=0.05）。我们的结果突出了 KIBRA、MTNR1B 和 FKBP5 在理解谵妄、认知和睡眠之间复杂关系中的相关性，这需要在更大、更多样化的人群中进一步研究。
