• Open Access

Detection of Three Genetic Polymorphisms in the 5′-Flanking Region and Intron 1 of Human CYP1A2 in the Japanese Population

Authors

  • Michihiro Chida,

    1. Laboratory of Drug Metabolism, Division of Pharmacobio-dynamics, Graduate School of Pharmaceutical Sciences, Hokkaido University, N12W6, Kita-ku, Sapporo 060-0812
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  • Tsuyoshi Yokoi,

    1. Laboratory of Drug Metabolism, Division of Pharmacobio-dynamics, Graduate School of Pharmaceutical Sciences, Hokkaido University, N12W6, Kita-ku, Sapporo 060-0812
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    • Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934.

  • Takafumi Fukui,

    1. Otsuka Assay Laboratories, Otsuka Pharmaceutical Co., 224-18 Aza Ebisuno Hiraishi, Kawauchi-cho, Tokushima 771-0130
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  • Moritoshi Kinoshita,

    1. Otsuka Assay Laboratories, Otsuka Pharmaceutical Co., 224-18 Aza Ebisuno Hiraishi, Kawauchi-cho, Tokushima 771-0130
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  • Jun Yokota,

    1. Biology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045
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  • Tetsuya Kamataki

    Corresponding author
    1. Laboratory of Drug Metabolism, Division of Pharmacobio-dynamics, Graduate School of Pharmaceutical Sciences, Hokkaido University, N12W6, Kita-ku, Sapporo 060-0812
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Abstract

Interindividual variability of the activity of CYP1A2 may be expected to affect cancer susceptibility, since the enzyme is capable of activating several carcinogens. In the present study, we found three new polymorphisms in the 5′-flanking region (CYP1A2/B) and intron 1 (CYP1A2/C and CYP1A2/D) of CYP1A2 in Japanese by using polymerase chain reaction-single strand conformation polymorphism. We developed methods to detect these polymorphisms by polymerase chain reaction-restriction fragment length polymorphism and performed a population study (159 subjects) to estimate the frequencies of the alleles. The frequencies of the CYP1A2/A (adenine), CYP1A2/B (thymine-deleted), CYP1A2/C (guanine) and CYP1A2/D (adenine) variants were 21.1, 42.0, 8.2 and 61.3%, respectively. The results of family study supported the idea that these CYP1A2 genotypes are inherited with an autosomal codominant transmission.

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