title: The uridine diphosphate glucuronosyltransferase 2B15 D85Y and 2B17 deletion polymorphisms predict the glucuronidation pattern of androgens and fat mass in men.
abstract: BACKGROUND
  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 D85Y and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition.
  
  
  METHODS
  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.
  
  
  METHODS
  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-3alpha,17beta-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-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 D85Y 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.
authors: Center for Bone Research at the Sahlgrenska Academy, Department of Internal Medicine, Göteborg University, SE-41345 Göteborg, Sweden.
authors: Charlotte
authors: C
authors: Swanson
authors: Dan
authors: D
authors: Mellström
authors: Mattias
authors: M
authors: Lorentzon
authors: Liesbeth
authors: L
authors: Vandenput
authors: Jenny
authors: J
authors: Jakobsson
authors: Anders
authors: A
authors: Rane
authors: Magnus
authors: M
authors: Karlsson
authors: Osten
authors: O
authors: Ljunggren
authors: Ulf
authors: U
authors: Smith
authors: Anna-Lena
authors: AL
authors: Eriksson
authors: Alain
authors: A
authors: Bélanger
authors: Fernand
authors: F
authors: Labrie
authors: Claes
authors: C
authors: Ohlsson
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity / Q000235:genetics* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D000728:Androgens / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D020719:Glucuronides / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics*; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000652:urine; D006801:Humans; D007328:Insulin / Q000097:blood / Q000652:urine; D007333:Insulin Resistance; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism / Q000652:urine
chemical_list: D000728:Androgens; D001786:Blood Glucose; D020719:Glucuronides; D012739:Gonadal Steroid Hormones; D007328:Insulin; D012738:Sex Hormone-Binding Globulin; D014453:Glucuronosyltransferase