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US 2006/0216738 A1Published application
SNPs in 5' regulatory region of MDR1 gene
OwnerMorimasa Wada, Michihiko Kuwanoinventors
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OwnerMorimasa Wada, Michihiko Kuwanoinventors
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The present invention relates to a method for determining haplotypes or diplotypes of a MDR1 gene targeting the 5′ upstream regulatory region of MDR1 gene encoding P-gp, an ABC transporter which is may be expressed in the apical membrane side and may transport a wide range of substrates. By detecting a polymorphism at −934 and/or −692, in addition to a position selected from −2903, −2410, −2352, −1910, −1717, and −1325 in a nucleotide sequence of the 5′ upstream regulatory region of MDR1 gene, haplotypes or diplotypes of the 5′upstream regulatory region of MDR1 gene may be determinable. The above positions to detect polymorphism are indicated in relation to a first base of ATG start codon which is set to +1. ATG start codon is located in exon 2, and the transcription start site corresponds to −699 in this numbering system.
A method for determining haplotypes and/or diplotypes of a 5′regulatory region of MDR1 gene, by detecting a polymorphism at a position selected from −2903, −2410, −2352, −1910, −1717 and −1325, and optionally by detecting polymorphism at a position selected from −934 and/or −692 position, when the position is indicated in relation to a first base of translation start codon (ATG) which is set to +1, in a nucleotide sequence of a 5′regulatory region of a MDR1 gene.
A DNA of 5′ regulatory region of MDR1 gene, wherein bases at −2410, −2352, −1910, −934, −692 are replaced with thymine, adenine, thymine, adenine, thymine, respectively, when the position is indicated in relation to a first base of translation start codon (ATG) which is set to +1, in a nucleotide sequence of a 5′regulatory region of MDR1 gene, or a DNA of 5′regulatory region of MDR1 gene, wherein bases at −2410, −2352, −1910, −934, −692 are replaced with cytosine, guanine, cytosine, guanine, cytosine, respectively, when the position is indicated in relation to a first base of translation start codon (ATG) which is set to +1, in a nucleotide sequence of a 5′regulatory region of MDR1 gene, or a DNA of 5′ regulatory region of MDR1 gene, wherein bases at −2410, −2352, −1910, −934, −692 are replaced with cytosine, adenine, cytosine, guanine, cytosine, respectively, when the position is indicated in relation to a first base of translation start codon (ATG) which is set to +1, in a nucleotide sequence of a 5′regulatory region of MDR1 gene, or a DNA of 5′ regulatory region of MDR1 gene, wherein bases at −2410, −2352, −1910, −934, −692 are replaced with thymine, adenine, thymine, guanine, thymine, respectively, when the position is indicated in relation to a first base of translation start codon (ATG) which is set to +1, in a nucleotide sequence of a 5′regulatory region of MDR1 gene.
A method for developing a drug for controlling MDR1 expression, wherein at least one position selected from −2903, −2410, −2352, −1910, −1717 and −1325, −934, −692 is targeted, when the position is indicated in relation to a first base of translation start codon (ATG) which is set to +1, in a nucleotide sequence of a 5′regulatory region of MDR1 gene.
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