The association between polymorphisms in the CYP17 and 5 alpha-reductase (SRD5A2) genes and serum androgen concentrations in men

Prospective studies suggest that prostate cancer risk may be increased in a ssociation with high serum concentrations of free testosterone and androsta nediol glucuronide (A-diol-g). Polymorphisms have been identified in the 17 -hydroxylase cytochrome P4,50 gene (CYP17) and the steroid 5 alpha -reducta se type II gene (SRD5A2), two genes that are involved in the biosynthesis a nd metabolism of androgens in men. The CYP17 MspA1 I polymorphism has been associated with increased prostate cancer risk, and the SRD5A2 V89L polymor phism has been associated with low A-diol-g in Asian men, a serum marker of Sa-reductase activity. The purpose of this study was to investigate the as sociation between these two polymorphisms and serum sex hormone concentrati ons in 621 British men. In particular, we wanted to test the hypotheses tha t the A2 allele in the CYP17 gene is associated with increased serum testos terone concentrations, and the L allele in the SRD5A2 gene is associated wi th reduced A-diol-g concentrations. Mean hormone concentrations were evalua ted in each genotype and adjusted for age and other relevant factors. We fo und no evidence that the CYP17 MsgA1 I polymorphism was associated with hig her testosterone levels. The L/L genotype of the SRD5A2 V89L polymorphism w as associated with a 10% lower A-diol-g concentration, but this was not sig nificant at the 5% level, However, the L/L genotype of the V89L polymorphis m was associated with significantly lower concentrations of testosterone an d free testosterone (by 12% and 16%, respectively) and an 8% higher sex hor mone-binding globulin concentration. These results suggest that the CYP17 M spA1 I polymorphism is not associated with testosterone concentrations and that the SRD5A2 V89L polymorphism is not a strong determinant of A-diol-g c oncentration in Caucasian men.