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学術誌査読

77 被引用数 (Scopus)


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.

ジャーナルJournal of Pharmacology and Experimental Therapeutics
出版ステータス出版済み - 12月 2004

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 薬理学


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