基因多态性与七氟醚麻醉诱导下催眠反应的关系。

Association between well-characterized gene polymorphisms and the hypnosis response caused by sevoflurane-induced anaesthesia.

机构信息

Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, China.

Hunan Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha, China.

出版信息

J Clin Pharm Ther. 2020 Dec;45(6):1442-1451. doi: 10.1111/jcpt.13275. Epub 2020 Oct 5.

DOI:10.1111/jcpt.13275

PMID:33016519

Abstract

WHAT IS KNOWN AND OBJECTIVE

Sevoflurane is the most widely used volatile anaesthetic in clinical practice. It exhibits a hypnotic (unconsciousness) effect and causes a loss of reaction to noxious stimuli (immobility). However, to date, the mechanism of action of sevoflurane is poorly understood. In this study, we explored the effects of genetic variations on sevoflurane-induced hypnosis.

METHODS

Sixty-six SNPs in 18 candidate genes were genotyped using MALDI-TOF MassARRAY in a discovery cohort containing 161 patients administered sevoflurane. Significant polymorphisms were assessed in a validation cohort containing 265 patients.

RESULTS AND DISCUSSION

Three polymorphisms (GRIN1 rs28681971, rs79901440 and CHRNA7 rs72713539) were significantly associated with the time to loss of consciousness in patients treated with sevoflurane in the discovery cohort; among them, GRIN1 rs28681971 showed a significant association even after false discovery rate (FDR) correction (p = 0.039). Following the validation analysis, GRIN1 rs28681971 and rs79901440 showed statistical efficacy (p = 0.027, 0.034). Combined assessments and meta-analysis of the results of the two cohorts indicated that the C carriers of rs28681971 and T carriers of rs79901440 in GRIN1 require a longer time to achieve unconsciousness.

WHAT IS NEW AND CONCLUSION

These findings suggest that GRIN1 polymorphisms are associated with sevoflurane-induced unconsciousness. Thus, the genotypes of GRIN1 may serve as novel and meaningful biomarkers for sevoflurane-induced unconsciousness.

摘要

已知和目的

七氟醚是临床实践中最广泛使用的挥发性麻醉剂。它具有催眠（无意识）作用，并导致对有害刺激（不动）失去反应。然而，迄今为止，七氟醚的作用机制仍知之甚少。在这项研究中，我们探讨了遗传变异对七氟醚诱导催眠的影响。

方法

在包含 161 名接受七氟醚治疗的患者的发现队列中，使用 MALDI-TOF MassARRAY 对 18 个候选基因中的 66 个 SNP 进行基因分型。在包含 265 名患者的验证队列中评估显著的多态性。

结果与讨论

在发现队列中，三种多态性（GRIN1 rs28681971、rs79901440 和 CHRNA7 rs72713539）与接受七氟醚治疗的患者意识丧失时间显著相关；其中，GRIN1 rs28681971 甚至在假发现率（FDR）校正后仍具有显著相关性（p = 0.039）。在验证分析后，GRIN1 rs28681971 和 rs79901440 显示出统计学疗效（p = 0.027，0.034）。对两个队列的结果进行综合评估和荟萃分析表明，GRIN1 中的 rs28681971 的 C 携带者和 rs79901440 的 T 携带者需要更长的时间才能达到无意识状态。