Systematic functional characterization of cytochrome P450 2E1 promoter variants in the Chinese Han population

CYP2E1 promoter polymorphisms can lead to significant interindividual differences in expression of CYP2E1. Using a database of CYP2E1 gene polymorphisms established in 2010, our study aimed to functionally characterize the single nucleotide polymorphisms (SNPs) of the promoter region and correspondi...

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Bibliographic Details
Published in:PloS one 2012-07, Vol.7 (7), p.e40883
Main Authors: Huang, Xunyi, Chen, Lili, Song, Wenlong, Chen, Ling, Niu, Jiamin, Han, Xia, Feng, Guoyin, He, Lin, Qin, Shengying
Format: Article
Language:English
Subjects:
Adenoviruses
Alcohol
Analysis
Asian Continental Ancestry Group - genetics
Binding Sites - genetics
Biology
China
Cloning
CYP2E1 gene
Cytochrome
Cytochrome P-450
Cytochrome P-450 CYP2E1 - genetics
Cytochrome P450
Cytokines
Education
Enzymes
Ethanol
Ethnic Groups - genetics
Gene expression
Genes
Genes, Reporter
Genetic aspects
Genetics
Genetics, Population
Genomics
Haplotypes
Haplotypes - genetics
Hep G2 Cells
Humans
Laboratories
Liver diseases
Luciferase
Luciferases - metabolism
Medicine
Mutagenesis
Mutagenesis, Site-Directed
Mutation
Polymorphism
Polymorphism, Single Nucleotide - genetics
Population
Precision medicine
Promoter Regions, Genetic
Restriction Mapping
Rodents
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Site-directed mutagenesis
Software
Transcription factors
Transcription Factors - metabolism
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Summary:CYP2E1 promoter polymorphisms can lead to significant interindividual differences in expression of CYP2E1. Using a database of CYP2E1 gene polymorphisms established in 2010, our study aimed to functionally characterize the single nucleotide polymorphisms (SNPs) of the promoter region and corresponding haplotypes in the Chinese Han population. Six novel SNPs and seven haplotypes with a frequency equal to or greater than 0.01 were constructed on a luciferase reporter system on the basis of site-directed mutagenesis. Dual luciferase reporter systems were used to analyze regulatory activity. The constructs including single novel SNP mutations exhibited insignificant change in luciferase activity, whereas, the activity produced by Haplo1(GTTGCTATAT), Haplo2 (CTTGCTATAT) and Haplo7 (GAGCTCACAT), containing a -333T>A polymorphism was significantly greater than for the wild type in Hep G2 cells (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0040883