胆碱能系统基因变异与老年患者术后谵妄和认知功能障碍的关系。
Association between genetic variants of the cholinergic system and postoperative delirium and cognitive dysfunction in elderly patients.
机构信息
Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Berlin, Germany.
Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
出版信息
BMC Med Genomics. 2021 Oct 21;14(1):248. doi: 10.1186/s12920-021-01071-1.
BACKGROUND
Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are frequent and serious complications after surgery. We aim to investigate the association between genetic variants in cholinergic candidate genes according to the Kyoto encyclopedia of genes and genomes - pathway: cholinergic neurotransmission with the development of POD or POCD in elderly patients.
METHODS
This analysis is part of the European BioCog project ( www.biocog.eu ), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental-State-Examination score ≤ 23 points were excluded. POD was assessed up to seven days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method and a patient chart review. POCD was assessed three months after surgery with a neuropsychological test battery. Genotyping was performed on the Illumina Infinium Global Screening Array. Associations with POD and POCD were analyzed using logistic regression analysis, adjusted for age, comorbidities and duration of anesthesia (for POCD analysis additionally for education). Odds ratios (OR) refer to minor allele counts (0, 1, 2).
RESULTS
745 patients could be included in the POD analysis, and 452 in the POCD analysis. The rate of POD within this group was 20.8% (155 patients), and the rate of POCD was 10.2% (46 patients). In a candidate gene approach three genetic variants of the cholinergic genes CHRM2 and CHRM4 were associated with POD (OR [95% confidence interval], rs8191992: 0.61[0.46; 0.80]; rs8191992: 1.60[1.22; 2.09]; rs2067482: 1.64[1.10; 2.44]). No associations were found for POCD.
CONCLUSIONS
We found an association between genetic variants of CHRM2 and CHRM4 and POD. Further studies are needed to investigate whether disturbances in acetylcholine release and synaptic plasticity are involved in the development of POD.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02265263.
背景
术后谵妄（POD）和术后认知功能障碍（POCD）是老年人手术后常见且严重的并发症。我们旨在根据京都基因与基因组百科全书 - 胆碱能神经递质通路：胆碱能神经递质，研究胆碱能候选基因的遗传变异与老年患者 POD 或 POCD 的发展之间的关系。
方法
本分析是欧洲生物认知项目（www.biocog.eu）的一部分，这是一项针对老年手术患者的前瞻性多中心观察性研究。排除 Mini-Mental-State-Examination 评分≤23 分的患者。使用护理谵妄筛查量表、意识模糊评估方法和患者病历回顾，在术后 7 天内评估 POD。术后三个月使用神经心理学测试套件评估 POCD。通过 Illumina Infinium Global Screening Array 进行基因分型。使用逻辑回归分析调整年龄、合并症和麻醉持续时间（对于 POCD 分析，另外根据教育程度进行调整），分析与 POD 和 POCD 的相关性。优势比（OR）表示次要等位基因数（0、1、2）。
结果
745 例患者可纳入 POD 分析，452 例患者可纳入 POCD 分析。该组中 POD 的发生率为 20.8%（155 例患者），POCD 的发生率为 10.2%（46 例患者）。在候选基因方法中，胆碱能基因 CHRM2 和 CHRM4 的三个遗传变异与 POD 相关（OR [95%置信区间]，rs8191992：0.61[0.46；0.80]；rs8191992：1.60[1.22；2.09]；rs2067482：1.64[1.10；2.44]）。未发现与 POCD 相关的遗传变异。
结论
我们发现 CHRM2 和 CHRM4 基因的遗传变异与 POD 之间存在关联。需要进一步的研究来调查乙酰胆碱释放和突触可塑性的紊乱是否参与 POD 的发展。
试验注册
ClinicalTrials.gov：NCT02265263。
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