Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene

Hiroshi Takane, Daisuke Kobayashi, Takeshi Hirota, Junzo Kigawa, Naoki Terakawa, Kenji Otsubo, Ichiro Ieiri

研究成果: ジャーナルへの寄稿記事

74 引用 (Scopus)

抄録

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 kilo-bases), 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.

元の言語英語
ページ(範囲)1179-1187
ページ数9
ジャーナルJournal of Pharmacology and Experimental Therapeutics
311
発行部数3
DOI
出版物ステータス出版済み - 12 1 2004

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Genetic Promoter Regions
Haplotypes
Genes
Nucleotides
Multiple Drug Resistance
P-Glycoprotein
DNA Methylation
Luciferases
Reporter Genes
Real-Time Polymerase Chain Reaction
Transcription Factors
Binding Sites
Gene Expression
Messenger RNA
Mutation
Liver

All Science Journal Classification (ASJC) codes

  • Pharmacology

これを引用

Haplotype-oriented genetic analysis and functional assessment of promoter variants in the MDR1 (ABCB1) gene. / Takane, Hiroshi; Kobayashi, Daisuke; Hirota, Takeshi; Kigawa, Junzo; Terakawa, Naoki; Otsubo, Kenji; Ieiri, Ichiro.

:: Journal of Pharmacology and Experimental Therapeutics, 巻 311, 番号 3, 01.12.2004, p. 1179-1187.

研究成果: ジャーナルへの寄稿記事

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AU - Kigawa, Junzo

AU - Terakawa, Naoki

AU - Otsubo, Kenji

AU - Ieiri, Ichiro

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