CYP3A4 * 1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients

Jing Jing Yuan, Jun Kai Hou, Wei Zhang, Yan Zi Chang, Zhi Song Li, Zong Yu Wang, Ying Ying Du, Xiao Jing Ma, Li Rong Zhang, Quan Cheng Kan, Keith A Candiotti

Research output: Contribution to journalArticle

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Abstract

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 of fentanyl (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.

Original languageEnglish (US)
Pages (from-to)55-60
Number of pages6
JournalPharmacology
DOIs
StateAccepted/In press - Jun 12 2015
Externally publishedYes

Fingerprint

Cytochrome P-450 CYP3A
Liver Microsomes
Fentanyl
Genetic Polymorphisms
Alleles
Messenger RNA
Liver
Restriction Fragment Length Polymorphisms
High Pressure Liquid Chromatography
Pathology
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pharmacology

Cite this

CYP3A4 * 1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients. / Yuan, Jing Jing; Hou, Jun Kai; Zhang, Wei; Chang, Yan Zi; Li, Zhi Song; Wang, Zong Yu; Du, Ying Ying; Ma, Xiao Jing; Zhang, Li Rong; Kan, Quan Cheng; Candiotti, Keith A.

In: Pharmacology, 12.06.2015, p. 55-60.

Research output: Contribution to journalArticle

Yuan, JJ, Hou, JK, Zhang, W, Chang, YZ, Li, ZS, Wang, ZY, Du, YY, Ma, XJ, Zhang, LR, Kan, QC & Candiotti, KA 2015, 'CYP3A4 * 1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients', Pharmacology, pp. 55-60. https://doi.org/10.1159/000433441
Yuan, Jing Jing ; Hou, Jun Kai ; Zhang, Wei ; Chang, Yan Zi ; Li, Zhi Song ; Wang, Zong Yu ; Du, Ying Ying ; Ma, Xiao Jing ; Zhang, Li Rong ; Kan, Quan Cheng ; Candiotti, Keith A. / CYP3A4 * 1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients. In: Pharmacology. 2015 ; pp. 55-60.
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abstract = "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 of fentanyl (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.",
author = "Yuan, {Jing Jing} and Hou, {Jun Kai} and Wei Zhang and Chang, {Yan Zi} and Li, {Zhi Song} and Wang, {Zong Yu} and Du, {Ying Ying} and Ma, {Xiao Jing} and Zhang, {Li Rong} and Kan, {Quan Cheng} and Candiotti, {Keith A}",
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T1 - CYP3A4 * 1G Genetic Polymorphism Influences Metabolism of Fentanyl in Human Liver Microsomes in Chinese Patients

AU - Yuan, Jing Jing

AU - Hou, Jun Kai

AU - Zhang, Wei

AU - Chang, Yan Zi

AU - Li, Zhi Song

AU - Wang, Zong Yu

AU - Du, Ying Ying

AU - Ma, Xiao Jing

AU - Zhang, Li Rong

AU - Kan, Quan Cheng

AU - Candiotti, Keith A

PY - 2015/6/12

Y1 - 2015/6/12

N2 - 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 of fentanyl (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.

AB - 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 of fentanyl (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.

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