The uridine diphosphate glucuronosyltransferase 2B15 D85Y and 2B17 deletion polymorphisms predict the glucuronidation pattern of androgens and fat mass in men.
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.
Swanson
Charlotte
C
Center for Bone Research at the Sahlgrenska Academy, Department of Internal Medicine, Göteborg University, SE-41345 Göteborg, Sweden.
Mellström
Dan
D
Lorentzon
Mattias
M
Vandenput
Liesbeth
L
Jakobsson
Jenny
J
Rane
Anders
A
Karlsson
Magnus
M
Ljunggren
Osten
O
Smith
Ulf
U
Eriksson
Anna-Lena
AL
Bélanger
Alain
A
Labrie
Fernand
F
Ohlsson
Claes
C
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
D000728:Androgens; D001786:Blood Glucose; D020719:Glucuronides; D012739:Gonadal Steroid Hormones; D007328:Insulin; D012738:Sex Hormone-Binding Globulin; D014453:Glucuronosyltransferase