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

doi:10.3969/j.issn.1673-8640.2023.05.003

检验医学 ›› 2023, Vol. 38 ›› Issue (5): 419-423.DOI: 10.3969/j.issn.1673-8640.2023.05.003

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

苏曦¹, 周琰¹(), 黄剑², 高姚怡¹, 李懿皞¹, 王蓓丽¹, 潘柏申¹, 郭玮¹

1.复旦大学附属中山医院检验科，上海 200032
2.复旦大学附属中山医院麻醉科，上海 200032

收稿日期:2022-11-10 修回日期:2023-03-01 出版日期:2023-05-30 发布日期:2023-08-07
通讯作者: 周琰， E-mail：zhouyan3@zs-hospital.sh.cn。
作者简介:苏曦，女，1978年生，学士，主管技师，主要从事临床分子诊断学相关研究。
基金资助:
国家自然科学基金面上项目(81972000);国家自然科学基金面上项目(82172348);国家自然科学基金青年项目(81902139);上海市临床重点专科建设项目(shslczdzk03302);厦门市医疗卫生重点项目(YDZX20193502000002)

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

SU Xi¹, ZHOU Yan¹(), HUANG Jian², GAO Yaoyi¹, LI Yihao¹, WANG Beili¹, PAN Baishen¹, GUO Wei¹

1. Department of Clinical Laboratory，Zhongshan Hospital，Fudan University，Shanghai 200032，China
2. Department of Anesthesiology，Zhongshan Hospital，Fudan University，Shanghai 200032，China

Received:2022-11-10 Revised:2023-03-01 Online:2023-05-30 Published:2023-08-07

摘要/Abstract

摘要：

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13.99 μg [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。

关键词: CYP3A4 *1G, 芬太尼, 剂量, 麻醉后复苏观察室, 镇痛泵自控静脉镇痛, 风险因素

Abstract:

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 13.99 μg 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.

Key words: CYP3A4 *1G, Fentanyl, Dose, Post-anesthesia care unit, Patient-controlled intravenous analgesia, Risk factor

中图分类号:

R446.1

苏曦, 周琰, 黄剑, 高姚怡, 李懿皞, 王蓓丽, 潘柏申, 郭玮. 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[J]. 检验医学, 2023, 38(5): 419-423.

SU Xi, ZHOU Yan, HUANG Jian, GAO Yaoyi, LI Yihao, WANG Beili, PAN Baishen, GUO Wei. Effect of CYP3A4 *1G polymorphism on fentanyl in patients undergoing laparoscopic radical resection of colorectal cancer[J]. Laboratory Medicine, 2023, 38(5): 419-423.

图/表 4

参考文献 17

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基因位点	正向引物序列（5'~3'）	反向引物序列（5'~3'）
CYP3A4 *1G（rs2242480）	CAAGGAACACACCCATAACACT	TAGAAAGCAGATGAACCAGAGC
CYP3A5 *3（rs776746）	GTCCTTGTGAGCACTTGATG	AGCCCGATTCTGCAGCTGGA
COMT V158M（rs4680）	ACAGGCAAGATCGTGGACGC	CACCTTGGCAGTTTACCCAG
OPRM1 A118G（rs563649）	TTGGACTTTAAATATGGCAA	CATACATTGGAAATACTTAG

基因位点	正向引物序列（5'~3'）	反向引物序列（5'~3'）
CYP3A4 *1G（rs2242480）	CAAGGAACACACCCATAACACT	TAGAAAGCAGATGAACCAGAGC
CYP3A5 *3（rs776746）	GTCCTTGTGAGCACTTGATG	AGCCCGATTCTGCAGCTGGA
COMT V158M（rs4680）	ACAGGCAAGATCGTGGACGC	CACCTTGGCAGTTTACCCAG
OPRM1 A118G（rs563649）	TTGGACTTTAAATATGGCAA	CATACATTGGAAATACTTAG

CYP3A4 *1G 基因型	例数	年龄/岁	性别		体重/kg	身高/cm	芬太尼剂量
CYP3A4 *1G 基因型	例数	年龄/岁	男/例	女/例	体重/kg	身高/cm	PACU/μg	术后24 h PCIA/μg
11	50	60.74±5.95	25	25	63.42±8.91	162.86±8.12	50.40±22.15	134.90±56.55
11G+1G1G	51	58.73±5.40	33	18	64.36±8.80	166.37±6.82	37.65±26.73^*	112.55±46.70^*

CYP3A4 *1G 基因型	例数	年龄/岁	性别		体重/kg	身高/cm	芬太尼剂量
CYP3A4 *1G 基因型	例数	年龄/岁	男/例	女/例	体重/kg	身高/cm	PACU/μg	术后24 h PCIA/μg
11	50	60.74±5.95	25	25	63.42±8.91	162.86±8.12	50.40±22.15	134.90±56.55
11G+1G1G	51	58.73±5.40	33	18	64.36±8.80	166.37±6.82	37.65±26.73^*	112.55±46.70^*

项目	β值（95% CI）	P值
年龄	0.93（0.54~1.80）	0.038
性别
男	基准	0.850
女	0.99（-9.25~11.24）
体重	0.12（-0.45~0.68）	0.688
升高	-0.31（-0.97~0.36）	0.366
术中芬太尼用量	2.57（0.16~4.98）	0.039
手术时间	3.72（-5.92~13.36）	0.451
CYP3A4 *1G		0.001
11	基准
11G+1G1G	-16.75（-26.34~-7.17）
OPRM1 A118G		0.013
GG	基准
GA+AA	16.90（3.78~30.03）
COMT V158M		0.730
GG	基准
GA+AA	-1.79（-11.93~8.35）
CYP3A5 *3		0.037
GG	基准
GA+AA	10.65（0.69~20.60）

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

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