The uridine diphosphate glucuronosyltransferase 2B15 (DY)-Y-85 and 2B17 deletion Polymorphisms predict the glucuronidation pattern of androgens and fat mass in men
(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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- author
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 92
- issue
- 12
- pages
- 4878 - 4882
- publisher
- Oxford University Press
- external identifiers
-
- wos:000251399700058
- scopus:36849091940
- ISSN
- 1945-7197
- DOI
- 10.1210/jc.2007-0359
- language
- English
- LU publication?
- yes
- id
- ba13aaa9-5e7f-46ac-929d-efcdc693948a (old id 968626)
- date added to LUP
- 2016-04-01 16:43:56
- date last changed
- 2024-05-24 11:38:08
@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 < 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.}}, 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 = {{Oxford University Press}}, 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}}, doi = {{10.1210/jc.2007-0359}}, volume = {{92}}, year = {{2007}}, }