Department of Anesthesiology, Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
Department of Anesthesiology, the First Affiliated Hospital of University of South China, Hengyang, Hunan, 421000, China.
Sci Rep. 2017 Jun 13;7(1):3343. doi: 10.1038/s41598-017-03229-3.
Significant individual susceptibility to intravenous anesthetic propofol exists. The etiology of individual variability in the response to propofol may be influenced by genetic polymorphisms in metabolic and functional pathways. With current pharmacogenetics and modern molecular biology technologies, it is possible to study the influence of genetic polymorphisms on susceptibility to propofol. When inducing general anesthesia with intravenous propofol, high individual susceptibility to propofol was found. Using Sequenom MassARRAY single-nucleotide polymorphism (SNP) genotyping, we identified a mutation (rs6313) in the 5HT2A gene that was correlated to individual susceptibility to propofol effect-site concentration (Cep) and onset time of propofol induction. Carriers of the minor allele (G) of 5HT2A rs6313 required less propofol (20% decrease in Cep) and less time (40% decrease in onset time) to induce anesthesia. Moreover, associations were found between the gamma-aminobutyric acid (GABA) receptor SNP rs2279020 and the SCN9A SNP rs6746030 and the susceptibility of bispectral index (BIS) after propofol-induced anesthesia. In addition, dominant mutations in GABAA1 rs2279020, GABAA2 rs11503014, and CHRM2 rs1824024 were putatively associated with cardiovascular susceptibility to propofol anesthesia. No gene-gene interactions were found through a standardized measure of linkage disequilibrium and a multifactor dimensionality reduction analysis. Our results suggest that genetic polymorphisms related to mechanisms of propofol anesthesia are involved in propofol susceptibility.
个体对静脉麻醉异丙酚的敏感性存在显著差异。异丙酚反应个体差异的病因可能受代谢和功能途径中遗传多态性的影响。通过当前的药物遗传学和现代分子生物学技术，可以研究遗传多态性对异丙酚易感性的影响。在使用静脉注射异丙酚诱导全身麻醉时，发现个体对异丙酚的敏感性很高。通过使用 Sequenom MassARRAY 单核苷酸多态性（SNP）基因分型，我们在 5HT2A 基因中发现了一个与异丙酚效应部位浓度（Cep）和异丙酚诱导起始时间个体易感性相关的突变（rs6313）。5HT2A rs6313 的次要等位基因（G）携带者需要较少的异丙酚（Cep 减少 20%）和较短的时间（诱导麻醉的起始时间减少 40%）。此外，还发现γ-氨基丁酸（GABA）受体 SNP rs2279020 和 SCN9A SNP rs6746030 与异丙酚诱导麻醉后双频谱指数（BIS）的易感性之间存在关联。此外，GABAA1 rs2279020、GABAA2 rs11503014 和 CHRM2 rs1824024 的显性突变被推测与异丙酚麻醉的心血管易感性相关。通过标准化连锁不平衡测量和多因素降维分析未发现基因-基因相互作用。我们的结果表明，与异丙酚麻醉机制相关的遗传多态性参与了异丙酚的敏感性。
