Background: The clinical efficacy of fentanyl for pain control differs greatly across individuals. The purpose of this study was to investigate the impact of CYP3A4*1G polymorphism including wild-type homozygote (CYP3A4*1/*1, GG), mutant heterozygote (CYP3A4*1/*1G, GA), and mutant homozygote (CYP3A4*1G/*1G, AA) on fentanyl analgesia in Chinese patients undergoing hysteroscopy by the assessment of analgesia nociception index (ANI).
Methods: A total of 200 gynecologic patients scheduled for elective hysteroscopy under general anesthesia at Peking University People's Hospital from May to December in 2017 were enrolled in this study. Venous blood was withdrawn for genotyping of CYP3A4*1G before operation. Fentanyl 1 μg/kg was administered preoperatively followed by target-controlled infusion of propofol for induction and maintenance. Intraoperative analgesic efficacy of fentanyl was assessed by ANI monitoring at T0 (entering room), T1 (cervical dilation), T2 (start of cervical aspiration), and T3 (end of cervical aspiration) time points. The duration of propofol infusion and total dosage of propofol were recorded as well.
Results: The patients were divided into three groups according to CYP3A4*1G polymorphism, including 143 in GG group, 47 in GA group, and 10 in AA group. There was no significant difference in clinical demographics among three groups. The frequency of CYP3A4*1G variant alleles accounted for 16.8% and the distribution of variant alleles was consistent with Hardy-Weinberg equilibrium. Using a multilevel model, ANI values at T1 (63.81 ± 19.61), T2 (63.63 ± 17.82), and T3 (65.68 ± 17.79) were significantly lower than that at T0 (77.16 ± 12.93) in the study population (F = 23.50, P < 0.001), suggesting that higher levels of pain at T1, T2, and T3 than T0. Patients with GG genotype showed significantly lower ANI than those with GA or AA genotypes during hysteroscopy under the same dose of fentanyl.
Conclusion: CYP3A4*1G polymorphism associated with the analgesic efficacy of intraoperative fentanyl in the patients undergoing hysteroscopy under general anesthesia.
通过镇痛-伤害性刺激指数 (ANI) 评估CYP3A4*1G基因多态性对子宫镜检查患者芬太尼镇痛效应的影响 摘要 背景：芬太尼的临床镇痛疗效具有很大的个体差异。本研究的目的是采用镇痛-伤害性刺激指数（ANI），探讨CYP3A4*1G基因多态性（即野生型纯合子（CYP3A4*1/*1, GG）、突变型杂合子（CYP3A4*1/*1G, GA）和突变型纯合子（CYP3A4*1G/*1G, AA）对宫腔镜检查患者芬太尼镇痛效应的影响。 方法：本研究招募了200名2017年5月至12月期间在北京大学人民医院进行择期全身麻醉子宫镜检查的妇科患者。术前采集2 ml静脉血，用于CYP3A4*1G的基因分型。术前给与芬太尼1 μg/kg，以及异丙酚靶控输注作为诱导与维持。在T0（进入手术室）、T1（扩宫颈）、T2（清宫吸引开始）和T3（清宫吸引结束）时间点，通过ANI监测，评估芬太尼的术中镇痛效应。同时记录异丙酚输注的持续时间与总剂量。 结果：根据CYP3A4*1G的基因多态性，将200例手术患者随机分成3组：GG组143例、GA组47例、AA组10例。各组人口学资料无差异。CYP3A4*1G等位基因频率为16.8%，等位基因分布符合Hardy-Weinberg平衡（P> 0.05）。本研究采用了多水平模型，结果发现研究人群在T1(63.81 ± 19.61)、T2(63.63 ± 17.82)和 T3(65.68 ± 17.79)的ANI显著低于T0(77.16 ± 12.93, F=23.50, P <0.001)。在使用相同剂量的芬太尼时，子宫镜检查时GG组患者的ANI显著低于GA或AA组。 结论：CYP3A4*1G基因多态性与全身麻醉宫腔镜检查患者的术中芬太尼镇痛效果有关。.
Keywords: Analgesia; CYP3A4; Fentanyl; Genetic Polymorphism.