NDLI: CYP3A4*1G regulates CYP3A4 intron 10 enhancer and promoter activity in an allelic-dependent manner.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yang, Weihong Zhao, Dengzhi Han, Shengna Tian, Zengyuan Yan, Liang Zhao, Guoqiang Kan, Quancheng Zhang, Wei Zhang, Lirong
Abstract	OBJECTIVE: CYP3A41G (G > A) in human CYP3A4 intron 10 is associated with therapeutic effects of CYP3A4-metabolized drugs. The aim of this study was to predict its function in the regulation of CYP3A4 expression. METHODS: Functional analysis of the CYP3A41G allele was performed using bioinformatic methods and enhancer or promoter reporter assays in HepG2 cells. RESULTS: Transcription regulatory elements like CAATboxes, TATA-boxes, Sp1, SMARCA3.01, and Box II-like sequence were present in the intron 10 of CYP3A4. SMARCA3.01 and Box II-like sequence were responsible for differential binding of transcription factors on the CYP3A41G allele. In CYP3A41G, the G allele enhanced expression of the CYP3A4 promoter in a position-dependent and orientation-dependent manner, however, the A allele enhanced expression of the CYP3A4 promoter in a position-independent and orientation-independent manner. In addition, the G allele and the A allele both displayed strong transcriptional activation, but the latter showed higher promoter activity than the former. Also, the A allele showed greater activity than the CYP3A4 promoter. CONCLUSION: These results in vitro suggest that CYP3A4*1G regulates CYP3A4 intron 10 enhancer and promoter activity in an allelic-dependent manner.
File Format	HTM / HTML
ISSN	09461965
Issue Number	8
Volume Number	53
Journal	Int. Journal of Clinical Pharmacology and Therapeutics
Language	English
Publisher	Dustri-Verlag
Publisher Date	2015-08-01
Publisher Place	Germany
Access Restriction	Subscribed
Subject Keyword	Discipline Pharmacology Alleles Cytochrome P-450 Cyp3a Genetics Metabolism Enhancer Elements, Genetic Introns Promoter Regions, Genetic Base Sequence Binding Sites Computational Biology Gene Expression Regulation, Enzymologic Genes, Reporter Genotype Hep G2 Cells Humans Molecular Sequence Data Phenotype Transcription Factors Transcription, Genetic Transcriptional Activation Transfection Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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