TY - JOUR
T1 - SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density
AU - Eriksson, A. L.
AU - Lorentzon, M.
AU - Mellström, D.
AU - Vandenput, L.
AU - Swanson, C.
AU - Andersson, N.
AU - Hammond, G. L.
AU - Jakobsson, J.
AU - Rane, A.
AU - Orwoll, E. S.
AU - Ljunggren, Ö
AU - Johnell, O.
AU - Labrie, F.
AU - Windahl, S. H.
AU - Ohlsson, Claes
N1 - Funding Information:
This work was supported by the Swedish Research Council (Grants 04250 and 04496), the Swedish Foundation for Strategic Research, European Commission Grant QLK4-CT-2002-02528, the ALF/LUA (Avtal om Läkarutbildning och Forskning/Läkarutbildningsavtalet) research grant in Göteborg, the Lundberg Foundation, the Torsten and Ragnar Söderberg’s Foundation, Petrus and Augusta Hedlunds Foundation, the Novo Nordisk Foundation, The Göteborg Medical Society, and World Anti-Doping Agency.
PY - 2006/12
Y1 - 2006/12
N2 - Context: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. Objective: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)n microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. Design and Study Subjects: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n ≅3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). Main Outcome Measures: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5α-androstane-3α,17β-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. Results: In both cohorts, (TAAAA)n and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5α-androstane-3α,17β-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. Conclusions: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.
AB - Context: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. Objective: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)n microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. Design and Study Subjects: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n ≅3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). Main Outcome Measures: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5α-androstane-3α,17β-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. Results: In both cohorts, (TAAAA)n and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5α-androstane-3α,17β-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. Conclusions: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.
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U2 - 10.1210/jc.2006-0679
DO - 10.1210/jc.2006-0679
M3 - Article
C2 - 16926255
AN - SCOPUS:33845473304
SN - 0021-972X
VL - 91
SP - 5029
EP - 5037
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 12
ER -