Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-11-23
pubmed:abstractText
Recently, a number of nucleotide variants have been described in the multidrug resistance 1 (MDR1/ABCB1) gene; however, most studies have focused on the coding region. In the present study, we identified promoter variants of the MDR1 gene and evaluated their phenotypic consequences using a reporter gene assay and the real-time polymerase chain reaction method. Ten allelic variants were detected in the promoter region (approximately 2 kilobases), seven of which were newly identified. Certain mutations occurred simultaneously, and a total of 10 haplotypes were observed. These promoter polymorphisms were found more frequently in Japanese than Caucasians. Some haplotypes were associated with changes in luciferase activity and placental and hepatic mRNA levels. We also determined DNA methylation status in the proximal promoter region of the MDR1 gene. The promoter region around potential binding sites for transcription factors was found to be hypomethylated and thus likely to be independent of the gene expression. Nucleotide and/or haplotype variants not only in the coding region but also in the promoter region of the MDR1 gene may be important for interindividual differences of P-glycoprotein expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
311
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1179-87
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15280437-Adult, pubmed-meshheading:15280437-Asian Continental Ancestry Group, pubmed-meshheading:15280437-Base Sequence, pubmed-meshheading:15280437-Cells, Cultured, pubmed-meshheading:15280437-CpG Islands, pubmed-meshheading:15280437-DNA, pubmed-meshheading:15280437-Electrophoretic Mobility Shift Assay, pubmed-meshheading:15280437-European Continental Ancestry Group, pubmed-meshheading:15280437-Female, pubmed-meshheading:15280437-Genes, MDR, pubmed-meshheading:15280437-Genetic Variation, pubmed-meshheading:15280437-Haplotypes, pubmed-meshheading:15280437-Humans, pubmed-meshheading:15280437-Liver, pubmed-meshheading:15280437-Luciferases, pubmed-meshheading:15280437-Methylation, pubmed-meshheading:15280437-Molecular Sequence Data, pubmed-meshheading:15280437-Nuclear Proteins, pubmed-meshheading:15280437-Placenta, pubmed-meshheading:15280437-Plasmids, pubmed-meshheading:15280437-Pregnancy, pubmed-meshheading:15280437-Promoter Regions, Genetic, pubmed-meshheading:15280437-RNA, Messenger, pubmed-meshheading:15280437-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15280437-Transcription, Genetic
pubmed:year
2004
pubmed:articleTitle
Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene.
pubmed:affiliation
Department of Hospital Pharmacy, Faculty of Medicine, Tottori University, 36-1, Nishi-machi, Yonago, 683-8504, Japan. takane@grape.med.tottori-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't