CYP3A4*1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients
CYP3A4*1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients
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DOI：
10.1159/000433441
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发表时间：
2015-01-01
期刊：
影响因子：
3.1
通讯作者：
Candiotti, Keith A.
中科院分区：
文献类型：
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作者：
Yuan, Jing-Jing;Hou, Jun-Kai;Candiotti, Keith A.
目的：本研究旨在探讨CYP3A4*1G基因多态性是否影响中国人肝微粒体中芬太尼的代谢。方法：从88例接受肝切除手术的肝胆外科患者中提取人肝微粒体。从切除组织的外缘取正常肝脏样本（经病理部确认）。研究了芬太尼在人肝微粒体中的代谢。采用高效液相色谱法测定芬太尼的浓度。采用PCR限制性片段长度多态性方法对CYP3A4*1G变异等位基因进行分型。结果：88例中国肝胆外科患者中CYP3A4* 1G变异等位基因的频率为0.188。*1G /*1G纯合子患者芬太尼代谢率（0.85 +/- 0.37）显著低于*1/*1野生型患者（1.89 +/- 0.58）或*1/*1G杂合子患者（1.82 +/- 0.65,p < 0.05）。芬太尼代谢率无性别差异（p > 0.05），年龄与芬太尼代谢率无相关性（p > 0.05）。不同肝胆疾病患者芬太尼代谢率差异无统计学意义（p < 0.05）。不同CYP3A4*1G变异等位基因间CYP3A4 mRNA表达差异有统计学意义（p < 0.05）。CYP3A4 mRNA与芬太尼代谢率呈正相关（p < 0.01）。结论：CYP3A4*1G基因多态性降低芬太尼的代谢。CYP3A4 mRNA水平与芬太尼代谢呈正相关。(C) 2015 S. Karger AG，巴塞尔
Purpose:This study aimed to investigate whether CYP3A4*1G genetic polymorphism influences the metabolism of fentanyl in human liver microsomes in Chinese patients. Methods: The human liver microsomes were obtained from 88 hepatobiliary surgery patients who accepted liver resection surgery in this study. A normal liver sample (confirmed by the Department of Pathology) was taken from the outer edge of the resected tissue. The metabolism of fentanyl in human liver microsomes was studied. The concentration of fentanyl was measured by high performance liquid chromatography. The CYP3A4*1G variant allele was genotyped using the PCR restriction fragment length polymorphism method. Results: The frequency of the CYP3A4* 1G variant allele was 0.188 in the 88 Chinese patients who had received hepatobiliary surgery. The metabolic rate of fentanyl in patients homozygous for the * 1G/*1G variant (0.85 +/- 0.37) was significantly lower than that in patients bearing the wild-type allele * 1/*1 (1.89 +/- 0.58) or in patients heterozygous for the *1/*1G variant (1.82 +/- 0.65; p < 0.05). There were no gender-related differences in the metabolic rate of fentanyl (p > 0.05) nor was there any correlation between age and metabolic rate of fentanyl (p > 0.05). Results from different hepatobiliary diseases showed no significant difference in the metabolic rate of fentanyl (p > 0.05). The difference of CYP3A4 mRNA among different CYP3A4*1G variant alleles was significant (p < 0.05). There was positive correlation between CYP3A4 mRNA and metabolic rate offentanyl (p < 0.01). Conclusions: CYP3A4*1G genetic polymorphism decreases the metabolism of fentanyl. There is a positive correlation between CYP3A4 mRNA level and metabolism of fentanyl. (C) 2015 S. Karger AG, Basel