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

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 (pFDR = 0.039). Following the validation analysis, GRIN1 rs28681971 and rs79901440 showed statistical efficacy (pFDR = 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.

Mechanisms and implications in gene polymorphism mediated diverse reponses to sedatives, analgesics and muscle relaxants

“…details, individuals with the GRIN1 rs28681971 TT genotype took much less time to achieve the target depth of sevoflurane induced anesthesia than those with the TC genotype. And a longer time was spent to obtain the same sedation depth by individuals with the GRIN1 rs79901440 CT genotype than those with the CC genotype [42].…”

“…There is a glycine-binding site in GRIN1 subunit [46,47]. GRIN1 gene mutations (rs28681971 and rs79901440) may impact on the minimum free energy of the molecular's secondary structure, then disrupt the folding of GRIN1 protein and the function of NMDA receptor [42]. Thus, it is explainable that the action of sevoflurane varies among individuals with mutated GRIN1 genotype.…”

“…Chen et al [ 40 ] have systematically screened the molecular sites that might affect the pharmacological action of sevoflurane. They identified that the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) polymorphisms (rs28681971 and rs79901440) were intimately related to the time required for unconsciousness induced by sevoflurane.…”

Effects of sevoflurane exposure during different stages of pregnancy on the brain development of rat offspring

“…Anesthesia is an approach for eliminating pain and creating good surgical conditions during surgery or diagnostic examination. Among the anesthetics in current use, propofol, remifentanil, and sevoflurane have been widely applied in clinical practice [2][3][4]. At present, the effectiveness and relative safety of * Yong-gang Xie oybfxc@163.com sevoflurane in surgical anesthesia are recognized [5].…”