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Developmental regulation of CYP3A4 and CYP3A7 in Chinese Han population.

Authors
  • He, Hang1
  • Nie, Ya-Li2
  • Li, Jiang-Feng2
  • Meng, Xiang-Guang3
  • Yang, Wei-Hong2
  • Chen, Yu-Long4
  • Wang, Shu-Jie2
  • Ma, Xiaochao5
  • Kan, Quan-Cheng6
  • Zhang, Li-Rong7
  • 1 Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China; Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, PR China. , (China)
  • 2 Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China. , (China)
  • 3 Laboratory of Cardiovascular Disease and Drug Research, Zhengzhou No. 7 People's Hospital, Zhengzhou, Henan, PR China. , (China)
  • 4 The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, PR China. , (China)
  • 5 Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
  • 6 The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, PR China. Electronic address: [email protected] , (China)
  • 7 Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, PR China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Drug metabolism and pharmacokinetics
Publication Date
December 2016
Volume
31
Issue
6
Pages
433–444
Identifiers
DOI: 10.1016/j.dmpk.2016.08.008
PMID: 27727071
Source
Medline
Keywords
License
Unknown

Abstract

CYP3A4 and CYP3A7 are generally served as the major adult and fetal liver forms, respectively, and exhibited a developmental switch during liver maturation. The objective of this study was to explore the potential mechanisms associated with the developmental switch of CYP3A4 and CYP3A7 in the Chinese Han population. We analyzed CYP3A4/7, nuclear receptors, and epigenetic modifications in human liver samples. We found that the expression levels of CYP3A4 mRNA in adults were significantly higher than the levels in fetus. In contrast, CYP3A7 mRNA expression reached a maximal level at an estimated gestational age of 25 weeks and then substantially decreased during the first year after birth. We also found that the expression level of hepatocyte nuclear factor 4 alpha (HNF4A) was most associated with CYP3A4 expression in adult liver; whereas the expression level of glucocorticoid receptor (GR) was intensively correlated with CYP3A7 expression in fetal liver. Furthermore, we illustrated the dynamic changes of H3K4me2 and H3K27me3 in the developmental switch of CYP3A7 and CYP3A4. In summary, our data suggested that HNF4A and GR, and epigenetic changes of H3K4me2 and H3K27me3 are associated with the ontogenic expressions of CYP3A4/3A7 in the livers of the Chinese Han population.

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