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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.

AbstractBACKGROUND:
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.
AuthorsS L MacLeod, S Nowell, J Plaxco, N P Lang
JournalAnnals of surgical oncology (Ann Surg Oncol) Vol. 7 Issue 10 Pg. 777-82 (Dec 2000) ISSN: 1068-9265 [Print] United States
PMID11129427 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Glucuronosyltransferase
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Case-Control Studies
  • Glucuronosyltransferase (genetics)
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction (methods)
  • Polymorphism, Genetic
  • Prostatic Neoplasms (enzymology, genetics)

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