CYP3A4*1G多态性对行腹腔镜结肠癌根治术患者芬太尼剂量的影响

Effect of CYP3A4*1G polymorphism on fentanyl in patients undergoing laparoscopic radical resection of colorectal cancer

目的评估CYP3A4*1G多态性对行腹腔镜结肠癌根治术患者芬太尼剂量的影响。方法选取2018年7月—2020年4月复旦大学附属中山医院行芬太尼麻醉腹腔镜结肠癌根治术的患者101例,检测其CYP3A4*1G基因型。采用多重线性回归分析探讨CYP3A4*1G多态性与芬太尼剂量之间的关系。结果多重线性回归分析结果显示,年龄、术中芬太尼剂量和CYP3A4*1G、CYP3A5*3、OPRM1 A118G多态性是麻醉后复苏观察室(PACU)芬太尼剂量的影响因素(P<0.05)。校正年龄、性别、体重、身高、术中芬太尼用量、手术时间和OPRM1 A118G、CYP3A5*3、COMT V158M多态性后,CYP3A4*1G野生型(*1*1型)患者PACU芬太尼剂量较CYP3A4*1G突变型[*1*1G型(杂合型)和*1G*1G(纯合型)]患者增加13.99μg[β=-13.99,95%可信区间(CI)为-6.78~-1.20,P=0.035],CYP3A4*1G多态性与术后24 h镇痛泵自控静脉镇痛(PCIA)芬太尼剂量无关(β=-7.79,95%CI为-33.70~-18.11,P=0.557),与术后48 h PCIA芬太尼剂量也无关(β=-10.28,95%CI为-22.70~2.15,P=0.108)。与CYP3A4*1G野生型(*1*1型)患者比较,CYP3A4*1G突变型[*1*1G型(杂合型)和*1G*1G(纯合型)]患者PACU和术后24 h PCIA芬太尼剂量显著降低(P<0.05)。结论CYP3A4*1G多态性是PACU芬太尼剂量的独立影响因素。相对于野生型患者,突变型患者消耗较少剂量芬太尼即可获得相似的麻醉效果。

Objective To assess the effect of CYP3A4*1G polymorphism on the dose of fentanyl in patients undergoing laparoscopic radical resection of colorectal cancer.Methods Totally,101 patients receiving fentanyl anesthesia laparoscopic radical resection of colon tumors at Zhongshan Hospital of Fudan University between July 2018 and April 2020 were enrolled.CYP3A4*1G genotype was determined,and the relation between CYP3A4*1G polymorphism and the dose of fentanyl was evaluated by multiple linear regression analysis.Results The results of multiple linear regression analysis showed that age,intraoperative fentanyl dose and the polymorphisms of CYP3A4*1G,CYP3A5*3 and OPRM1 A118G were risk factors for the dose of fentanyl in post-anesthesia care unit(PACU)(P<0.05).After adjusting for age,sex,weight,height,intraoperative fentanyl dose,operation time and the polymorphisms of OPRM1 A118G,CYP3A5*3 and COMT V158M,CYP3A4*1G wild type(*1*1)was found to be a risk factor for increased fentanyl dose in PACU[β=-13.99,95%confidence interval(CI)-26.78--1.20,P=0.035].Compared to fentanyl dose in patients with CYP3A4*1G mutant genotypes[*1*1G(heterozygous)and*1G*1G(homozygous)],the wild type ones were 13.99μg higher.There was no correlation between CYP3A4*1G polymorphism and fentanyl dose in 24 h patient-controlled intravenous analgesia(PCIA)after operation(β=-7.79,95%CI-33.70--18.11,P=0.557),as well as that in 48 h PCIA after operation(β=-10.28,95%CI-22.70-2.15,P=0.108).Compared with CYP3A4*1G wild type(*1*1)patients,the PACU and fentanyl dose in 24 h PCIA after operation of patients with CYP3A4*1G mutant genotypes[*1*1G(heterozygous)and*1G*1G(homozygous)]were decreased(P<0.05).Conclusions CYP3A4*1G polymorphism is an independent factor for fentanyl dose.Compared with mutated type,the anesthetic effect may be similar to wild type subjects by consuming less fentanyl.