A common deletion in the uridine diphosphate glucuronyltransferase (UGT) 2B17 gene is a strong determinant of androgen excretion in healthy pubertal boys.
Journal: 2009/April - Journal of Clinical Endocrinology and Metabolism
ISSN: 1945-7197
Abstract:
BACKGROUND
Testosterone (T) is excreted in urine as water-soluble glucuronidated and sulfated conjugates. The ability to glucuronidate T and other steroids depends on a number of different glucuronidases (UGT) of which UGT2B17 is essential. The aim of the study was to evaluate the influence of UGT2B17 genotypes on urinary excretion of androgen metabolites in pubertal boys.
METHODS
A clinical study of 116 healthy boys aged 8-19 yr. UGT2B17 genotyping was performed using quantitative PCR. Serum FSH, LH, T, estradiol (E2), and SHBG were analyzed by immunoassays, and urinary levels of androgen metabolites were quantitated by gas chromatography/mass spectrometry in all subjects.
RESULTS
Ten of 116 subjects (9%) presented with a homozygote deletion of the UGT2B17 gene (del/del), whereas 52 and 54 boys were hetero- and homozygous carriers of the UGT2B17 gene (del/ins and ins/ins), respectively. None of the reproductive hormones were affected by UGT2B17 genotype. In all subjects, mean urinary T/epitestosterone ratio was 1.56 [1.14 (SD); 0.1-6.9 (range)] and unaffected by age or pubertal stage. Subjects with homozygous deletions of UGT2B17 had significantly lower urinary levels of T and 5alpha- and 5beta-androstanediol. Mean urinary T/epitestosterone was significantly reduced in del/del subjects [0.29 (0.30); 0.1-1.0 (range), P < 0.0001].
CONCLUSIONS
In pubertal boys, a common homozygous deletion in the UGT2B17 gene strongly affected urinary excretion pattern of androgen metabolites but did not influence circulating androgen levels.
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