Small effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men.
OBJECTIVE
The human androgen receptor (AR) contains a polyglutamine and a polyglycine stretch which are highly polymorphic and are coded respectively by a CAG and GGN repeat in exon 1 of the AR gene. Although the in vitro studies indicated a possible effect of the GGN repeat polymorphism on the AR gene transcription and clinical observations suggest that it might modulate the androgen action, its functional significance remains unclear. We wanted to assess whether the GGN repeat affects the serum testosterone levels in healthy men, which is the expected outcome through feedback regulation if it influences androgen action as has been shown to be the case for the CAG repeat.


METHODS
A population based cross-sectional cohort study including 1476 healthy young, middle-aged, and elderly men.


METHODS
Testosterone and LH levels were determined by immunoassay; free testosterone (FT) levels were calculated. Genotyping of the GGN repeat was performed using the sequencing technique.


RESULTS
The GGN repeat number was significantly associated with circulating testosterone and FT levels (P=0.017 and P=0.013 respectively). However, taking into account that age, body mass index, and CAG are already in the regression model, the GGN repeat could explain only a small part of the variation of both testosterone and FT.


CONCLUSIONS
To our knowledge, this study is the first to demonstrate a significant positive association between the GGN repeat and androgen levels in a large cohort of healthy men. Although the present study thus adds credence to the view that the polyglycine tract in the AR can modulate AR action, this effect appears to be only small so that its clinical relevance remains questionable.
Bogaert
Veerle
V
Department of Endocrinology, 9 K12 I.E, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
Vanbillemont
Griet
G
Taes
Youri
Y
De Bacquer
Dirk
D
Deschepper
Ellen
E
Van Steen
Kristel
K
Kaufman
Jean-Marc
JM
D000328:Adult; D001483:Base Sequence; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics*; D013739:Testosterone / Q000097:blood*; D018911:Trinucleotide Repeats; D055815:Young Adult
D011944:Receptors, Androgen; D013739:Testosterone; D007986:Luteinizing Hormone