Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, China.
Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu 610041, China.
Biomed Pharmacother. 2022 Apr;148:112724. doi: 10.1016/j.biopha.2022.112724. Epub 2022 Feb 21.
The anesthesia sensitivity is heterogeneous both in animals and humans, while the underlying molecular mechanism has not yet been determined. Here, for the first time, we conducted a prospective observational study to test whether genetic variations contribute to the differential sensitivity to sevoflurane in humans.
Five hundred patients who underwent abdominal surgeries were included. The end-tidal sevoflurane concentration (ET) was adjusted to maintain Bispectral index (BIS) value between 40 and 60. The mean ET from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. These patients were further divided into high sensitivity group (mean - SD, H group) and low sensitivity group (mean + SD, L group) to investigate the genetic variants related to the differential sensitivity to sevoflurane by whole-exome sequencing (WES) and genome-wide association study (GWAS) in karyocyte from peripheral blood.
The mean ET of these 500 patients was 1.60% ± 0.34%. After pairing, 55 patients from H group and 59 patients from L group were selected for WES (ET of H group: 1.06% ± 0.13% vs. ET of L group: 2.17% ± 0.16%, P < 0.001), respectively. Finally, FAT atypical cadherin 2 (FAT2, SNP rs174272, rs174271, and rs174261), acireductone dioxygenase 1 (ADI1, SNP rs117278), NEDD4 E3 ubiquitin protein ligase (NEDD4, SNP rs70048, rs70049, and rs70056), and FAD dependent oxidoreductase domain containing 2 (FOXRED2, SNP rs144281) were found to be associated with sevoflurane sensitivity.
Genetic variations may contribute to the differential sensitivity to sevoflurane among humans.
动物和人类的麻醉敏感性存在异质性，但其潜在的分子机制尚未确定。在这里，我们首次进行了一项前瞻性观察研究，以测试遗传变异是否导致人类对七氟醚的敏感性不同。
纳入 500 名接受腹部手术的患者。调整呼气末七氟醚浓度（ET）以维持脑电双频指数（BIS）值在 40 至 60 之间。计算每位患者从气管插管后 20 分钟到手术开始后 2 小时的平均 ET。通过全外显子组测序（WES）和全基因组关联研究（GWAS），将这些患者进一步分为高敏感性组（平均值 ± 标准差，H 组）和低敏感性组（平均值 ± 标准差，L 组），以研究与七氟醚敏感性差异相关的遗传变异在外周血核细胞中。
500 名患者的平均 ET 为 1.60% ± 0.34%。配对后，从 H 组中选择 55 名患者，从 L 组中选择 59 名患者进行 WES（H 组 ET：1.06% ± 0.13% vs. L 组 ET：2.17% ± 0.16%，P < 0.001）。最后，发现 FAT 非典型钙黏蛋白 2（FAT2，SNP rs174272、rs174271 和 rs174261）、二氢乳清酸脱氢酶 1（ADI1，SNP rs117278）、NEDD4 E3 泛素蛋白连接酶（NEDD4，SNP rs70048、rs70049 和 rs70056）和 FAD 依赖氧化还原酶结构域包含蛋白 2（FOXRED2，SNP rs144281）与七氟醚敏感性相关。
遗传变异可能导致人类对七氟醚的敏感性不同。
