Ding Yuanyuan, Liu Aiqing, Wang Yafeng, Zhao Shuai, Huang Shiqian, Zhu Hongyu, Ma Lulin, Han Linlin, Shu Shaofang, Zheng Lidong, Chen Xiangdong
Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Anesthesiology, Lu'an Hospital Affiliated to Anhui Medical University, Lu'an, China.
Front Genet. 2023 Aug 24;14:1187415. doi: 10.3389/fgene.2023.1187415. eCollection 2023.
Dexmedetomidine (DXM) is widely used as an adjuvant to anesthesia or a sedative medicine, and differences in individual sensitivity to the drug exist. This study aimed to investigate the effect of genetic polymorphisms on these differences. A total of 112 patients undergoing hand surgery were recruited. DXM 0.5 μg/kg was administered within 10 min and then continuously injected (0.4 μg/kg/h). Narcotrend index, effective dose and onset time of sedation, MAP, and HR were measured. Forty-five single nucleotide polymorphisms (SNPs) were selected for genotype. We observed individual differences in the sedation and hemodynamics induced by DXM. rs2231142, rs16947, rs5758550, rs141294036, rs11739136, rs16934182, rs11046209, rs1800544, and rs1042713 were shown to cause statistically significant ( < 0.05) influence on the individual variation of DXM on sedation and hemodynamics. Moreover, the multiple linear regression analysis indicated sex, BMI, and rs1800544 are statistically related to the effective dose of DXM sedation. The evidence suggests that the nine SNPs involved in transport proteins, metabolic enzymes, and target proteins of DXM could explain the individual variability in the sedative and hemodynamic effects of DXM. Therefore, with SNP genotyping, these results could guide personalized medication and promote clinical and surgical management.
右美托咪定(DXM)被广泛用作麻醉辅助药物或镇静剂,且个体对该药物的敏感性存在差异。本研究旨在探讨基因多态性对这些差异的影响。共招募了112例接受手部手术的患者。在10分钟内静脉注射DXM 0.5μg/kg,然后持续输注(0.4μg/kg/h)。记录Narcotrend指数、镇静有效剂量和起效时间、平均动脉压(MAP)以及心率(HR)。选择45个单核苷酸多态性(SNP)进行基因分型。我们观察到DXM诱导的镇静和血流动力学存在个体差异。结果显示,rs2231142、rs16947、rs5758550、rs141294036、rs11739136、rs16934182、rs11046209、rs1800544和rs1042713对DXM在镇静和血流动力学方面的个体差异有统计学意义(<0.05)。此外,多元线性回归分析表明,性别、体重指数(BMI)和rs1800544与DXM镇静的有效剂量在统计学上相关。证据表明,涉及DXM转运蛋白、代谢酶和靶蛋白的9个SNP可以解释DXM在镇静和血流动力学效应方面的个体变异性。因此,通过SNP基因分型,这些结果可以指导个性化用药,并促进临床和手术管理。