An allele-specific polymerase chain reaction method for the determination of the D85Y polymorphism in the human UDP-glucuronosyltransferase 2B15 gene in a case-control study of prostate cancer.

BACKGROUND: UDP-glucuronosyltransferase 2B15 (UGT2B15) catalyzes the inactivation of dihydrotestosterone (DHT) by forming the DHT-glucuronide and is expressed in normal and hyperplastic prostate tissue. Alterations in the activity of this enzyme could be a major contributing factor to the bioavailability of androgens in target tissue such as the prostate.
METHODS: A polymorphism (D85 to Y85) has been identified in the UGT2B15 gene that results in a 50% reduction in enzyme activity. Previously, detection of the polymorphic nucleotide has required direct sequencing. We have developed and validated an allele-specific polymerase chain reaction (PCR) assay to identify the polymorphic base pair in the UGT2B15 gene. This assay was used to examine the distribution of the UGT2B15 polymorphism in a small case-control group (64 cases and 64 controls) from a prostate cancer study.
RESULTS: The results of this analysis show that prostate cancer patients were significantly more likely to be homozygous for the lower activity D85 UGT2B15 allele than control individuals (41% versus 19%, respectively, odds ratio = 3.0 (95% confidence intervals 1.3-6.5)).
CONCLUSIONS: These results suggest that individuals who are homozygous for the lower activity allele may be at increased risk for developing prostate cancer.