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

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.