SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density

A. L. Eriksson, M. Lorentzon, D. Mellström, L. Vandenput, C. Swanson, N. Andersson, G. L. Hammond, J. Jakobsson, A. Rane, Eric Orwoll, Ö Ljunggren, O. Johnell, F. Labrie, S. H. Windahl, Claes Ohlsson

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)5029-5037
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number12
DOIs
StatePublished - Dec 2006

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Pelvic Bones
Serum Globulins
Sex Hormone-Binding Globulin
Metabolites
Polymorphism
Bone Density
Androgens
Minerals
Bone
Genes
Androstane-3,17-diol
Dihydrotestosterone
Serum
Testosterone
Steroids
Genotype
Twin Studies
Sweden
Microsatellite Repeats
Femur

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density. / Eriksson, A. L.; Lorentzon, M.; Mellström, D.; Vandenput, L.; Swanson, C.; Andersson, N.; Hammond, G. L.; Jakobsson, J.; Rane, A.; Orwoll, Eric; Ljunggren, Ö; Johnell, O.; Labrie, F.; Windahl, S. H.; Ohlsson, Claes.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 12, 12.2006, p. 5029-5037.

Research output: Contribution to journalArticle

Eriksson, AL, Lorentzon, M, Mellström, D, Vandenput, L, Swanson, C, Andersson, N, Hammond, GL, Jakobsson, J, Rane, A, Orwoll, E, Ljunggren, Ö, Johnell, O, Labrie, F, Windahl, SH & Ohlsson, C 2006, 'SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density', Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 12, pp. 5029-5037. https://doi.org/10.1210/jc.2006-0679
Eriksson, A. L. ; Lorentzon, M. ; Mellström, D. ; Vandenput, L. ; Swanson, C. ; Andersson, N. ; Hammond, G. L. ; Jakobsson, J. ; Rane, A. ; Orwoll, Eric ; Ljunggren, Ö ; Johnell, O. ; Labrie, F. ; Windahl, S. H. ; Ohlsson, Claes. / SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 12. pp. 5029-5037.
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abstract = "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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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, Eric

AU - Ljunggren, Ö

AU - Johnell, O.

AU - Labrie, F.

AU - Windahl, S. H.

AU - Ohlsson, Claes

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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