Association between well-characterized gene polymorphisms and the hypnosis response caused by sevoflurane-induced anaesthesia
Autor: | Yu-Hao Xia, Ming-Hua Chen, You-Jie Zeng, Kai-Ming Duan, Wen Ouyang, Chao Fang, Sai-Ying Wang |
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Rok vydání: | 2020 |
Předmět: |
Adult
Candidate gene Time Factors Genotype medicine.drug_class Single-nucleotide polymorphism Nerve Tissue Proteins Bioinformatics 030226 pharmacology & pharmacy Polymorphism Single Nucleotide Receptors N-Methyl-D-Aspartate Sevoflurane Hypnotic Cohort Studies 03 medical and health sciences 0302 clinical medicine medicine Humans Pharmacology (medical) 030212 general & internal medicine Prospective Studies Pharmacology biology business.industry Unconsciousness GRIN1 Genetic Variation Cohort Anesthetics Inhalation biology.protein Biomarker (medicine) medicine.symptom business medicine.drug |
Zdroj: | Journal of clinical pharmacy and therapeuticsREFERENCES. 45(6) |
ISSN: | 1365-2710 |
Popis: | 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. |
Databáze: | OpenAIRE |
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