An Allele-Specific Polymerase Chain Reaction Method for the Determination of the D85Y Polymorphism in the Human UDPGlucuronosyltransferase 2B15 Gene in a Case-Control Study of Prostate Cancer

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Abstract
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 gene1 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 5 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.