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A functional C–G polymorphism in the CYP7B1 promoter region and its different distribution in Orientals and Caucasians

The Pharmacogenomics Journal volume 4, pages 245–250 (2004)Cite this article

Abstract

Cytochrome P450 (CYP) 7B1 is involved in many metabolic processes including androgen metabolism. Genetic variation in the CYP7B1 gene may play a role in predisposition to prostate cancer. Here, we screened the human CYP7B1 gene for possible polymorphisms. Only one single polymorphism was detected, a C–G change in the promoter –104 base pair from the transcription start site. The allele frequency was investigated in Swedish men and compared to a Korean population, as it is known that the frequency of prostate cancer is low among Orientals. We found that the frequency of the G-allele was 4.04% in Swedes (n=150) but only 0.33% among Koreans (n=153). Computer analysis indicated that the two variants bind with different affinities to a CCAAT-box binding protein. Expression studies with reporter constructs showed significantly higher transcriptional activity of the G variant in Hek293 cells (2.7-fold, P<0.05). In conclusion, we report here for the first time the detection of a single polymorphism in the CYP7B1 gene. This polymorphism is associated with phenotypic differences in an expression system and a widely different allele frequency in two ethnic populations, with great differences in the incidence of prostate cancer.

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Acknowledgements

This work was supported by grants from the Swedish Cancer Society, the World Anti-Doping Agency (WADA) and the Swedish Foundation for Strategic Research. Professor Ralf Morgenstern, Institute of Environmental Medicine, Karolinska Institute kindly provided HepG2 cells and Dr Mary Hunt, Department of Clinical Chemistry, Karolinska Institute kindly provided HEK293 cells.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden

    J Jakobsson, H Karypidis, A Rane & L Ekström

  2. Department of Urology, Örebro University Hospital, Örebro, Sweden

    J-E Johansson

  3. Department of Internal Medicine, Division of Clinical Pharmacology, Inha University Hospital, Inchon, Korea

    H-K Roh

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  1. J Jakobsson
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Correspondence to J Jakobsson.

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Jakobsson, J., Karypidis, H., Johansson, JE. et al. A functional C–G polymorphism in the CYP7B1 promoter region and its different distribution in Orientals and Caucasians. Pharmacogenomics J 4, 245–250 (2004). https://doi.org/10.1038/sj.tpj.6500236

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