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

Swanson, Charlotte; Mellstrom, Dan; Lorentzon, Mattias; Vandenput, Liesbeth; Jakobsson, Jenny; Rane, Anders; Karlsson, Magnus LU ; Ljunggren, Osten; Smith, Ulf and Eriksson, Anna-Lena, et al. (2007) In Journal of Clinical Endocrinology and Metabolism 92(12). p.4878-4882
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-... (More)
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. (Less)
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Journal of Clinical Endocrinology and Metabolism
volume
92
issue
12
pages
4878 - 4882
publisher
The Endocrine Society
external identifiers
  • wos:000251399700058
  • scopus:36849091940
ISSN
1945-7197
DOI
10.1210/jc.2007-0359
language
English
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yes
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ba13aaa9-5e7f-46ac-929d-efcdc693948a (old id 968626)
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2008-01-30 15:33:46
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2017-08-06 04:37:22
@article{ba13aaa9-5e7f-46ac-929d-efcdc693948a,
  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 &lt; 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 &lt; 0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity ( P &lt; 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.},
  author       = {Swanson, Charlotte and Mellstrom, Dan and Lorentzon, Mattias and Vandenput, Liesbeth and Jakobsson, Jenny and Rane, Anders and Karlsson, Magnus and Ljunggren, Osten and Smith, Ulf and Eriksson, Anna-Lena and Belanger, Alain and Labrie, Fernand and Ohlsson, Claes},
  issn         = {1945-7197},
  language     = {eng},
  number       = {12},
  pages        = {4878--4882},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {The uridine diphosphate glucuronosyltransferase 2B15 (DY)-Y-85 and 2B17 deletion Polymorphisms predict the glucuronidation pattern of androgens and fat mass in men},
  url          = {http://dx.doi.org/10.1210/jc.2007-0359},
  volume       = {92},
  year         = {2007},
}