细胞色素P450异构体CYP3A4^(*)1G基因多态性对老年直肠癌手术患者芬太尼用药量及术后镇痛效果的影响

Effect of cytochrome P450 isoform CYP3A4^(*)1G gene polymorphism on fentanyl dosage and postoperative analgesia in elderly patients with rectal cancer

目的探讨细胞色素P450异构体CYP3A4~*1G基因多态性对老年直肠癌手术患者芬太尼用药量及术后镇痛效果的影响。方法选取2016年2月至2018年5月于我院行直肠癌根治术的老年患者共173例,通过术前外周血PCR和测序评估CYP3A4~*1G的基因分型,对比CYP3A4~*1G突变(突变组)和野生型(野生组)患者其术中芬太尼用药量,采用视觉模拟评分(VAS)用于在术后不同时间点评估患者的疼痛程度,对比患者自控镇痛(PCA)的初次镇痛时间和术后24 h芬太尼使用量。结果在所有173例患者中,CYP3A4~*1G变异等位基因的频率为0.191,其中突变组共61例,野生组共112例。其中突变组术中使用的平均芬太尼药物总量显著低于野生组,差异具有统计学意义(t=7.662,P <0.001),突变组患者术后初次追加镇痛时间显著高于野生组(t=7.279,P <0.001),且突变组术后24 h芬太尼用量显著低于野生组(t=13.847,P <0.001),突变组在术后2、4和8 h的疼痛VAS评分均显著低于野生组(P <0.05)。结论 CYP3A4~*1G基因多态性在老年直肠癌手术麻醉中与芬太尼的药代动力学密切相关,CYP3A4~*1G遗传多态性可能是导致患者对芬太尼镇痛反应的个体差异的重要因素之一。

Objective To investigate the effect of cytochrome P450 isoform CYP3A4*1G gene polymorphism on the dose consumption of fentanyl and postoperative analgesia in elderly patients with rectal cancer.Methods A total of 173 elderly patients underwent.radical resection of rectal cancer from February 2016 to May 2018 were enrolled.The CYP3A4*1G genotyping was assessed by preoperative peripheral blood PCR and sequencing.The intraoperative fentanyl dose was compared between CYP3A4*1G mutation(mutation group)and wild type(wild group)patients,and visual analog scale(VAS)was used to assess the pain level at different time points after surgery.Initial analgesia time of analgesia(PCA)and fentanyl consumption were compared in the two groups after surgery for 24 hours.Results The frequency of the CYP3A4*1G variant allele was 0.191 in all 173 patients,including 61 in the mutation group and 112 in the wild group.The average amount of fentanyl used in the mutation group was significantly lower than that in the wild group,and the difference was statistically significant(t=7.662,P<0.001).The initial analgesia time in the mutation group was significantly higher than that in the wild group.(t=7.279,P<0.001),and the dose of fentanyl in the mutation group was significantly lower than that in the wild group(t=13.847,P<0.001).The pain VAS score in the mutation group was significantly lower than that in the wild group at 2 h,4 h and 8 h after surgery(P<0.05).Conclusion The CYP3A4*1G gene polymorphism is closely related to the pharmacokinetics of fentanyl in elderly patients with rectal cancer.The genetic polymorphism of CYP3A4*1G may be an important factor in the individual differences of the analgesic response to fentanyl.