The uridine diphosphate glucuronosyltransferase 2B15 (DY)-Y-85 and 2B17 deletion Polymorphisms predict the glucuronidation pattern of androgens and fat mass in men

Research output: Contribution to journalArticle

Abstract

Context: Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT) 2B15 and UGT2B17 glucuronidate androgens and their metabolites. Objective: Our objective was to determine in vivo whether the UGT2B15 (DY)-Y-85 and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition. Participants: Two population-based cohorts including young adult (n = 1068; age = 18.9 yr) and elderly ( n = 1001; age = 75.3 yr) men were included in the study. Main Outcome Measures: Serum and urine levels of testosterone ( T) and dihydrotestosterone (DHT) were measured by gas chromatography-mass spectrometry, and serum levels of the major glucuronidated androgen metabolites androstane-3 alpha, 17 beta- diol(androstanediol)-3-glucuronide, androstanediol-17-glucuronide, and androsterone-glucuronide were measured by liquid chromatography-tandem mass spectrometry. Body composition was measured by dual-energy x-ray absorptiometry. Results: Both the UGT2B15 D85Y and the UGT2B17 deletion polymorphisms were associated with serum levels of androstanediol-ediol-17-glucuronide (P < 0.001) but not with levels of androstanediol-3-glucuronide or androsterone-glucuronide in both cohorts. Glucuronidation of T and DHT was associated with the UGT2B17 deletion but not with the UGT2B15 (DY)-Y-85 polymorphism, suggested by strong associations between the deletion polymorphism and urine levels of these two hormones. Both polymorphisms were associated with several different measures of fat mass ( P < 0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity ( P < 0.05) as indicated by the homeostasis model assessment index. Conclusions: The UGT2B15 D85Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17- glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17- glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.

Details

Authors
  • Charlotte Swanson
  • Dan Mellstrom
  • Mattias Lorentzon
  • Liesbeth Vandenput
  • Jenny Jakobsson
  • Anders Rane
  • Magnus Karlsson
  • Osten Ljunggren
  • Ulf Smith
  • Anna-Lena Eriksson
  • Alain Belanger
  • Fernand Labrie
  • Claes Ohlsson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Orthopedics
Original languageEnglish
Pages (from-to)4878-4882
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number12
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes