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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.; Mellstrom, D.; Vandenput, L.; Swanson, C.; Andersson, N.; Hammond, G. L.; Jakobsson, J.; Rane, A. and Orwoll, E. S., et al. (2006) In Journal of Clinical Endocrinology and Metabolism 91(12). p.5029-5037
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 congruent to 3000; average age, 75.4 yr) and young adult men ( GOOD... (More)
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 congruent to 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, 5 alpha-androstane-3 alpha,17 beta-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 5 alpha-androstane-3 alpha,17 beta- 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. (Less)
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published
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Journal of Clinical Endocrinology and Metabolism
volume
91
issue
12
pages
5029 - 5037
publisher
The Endocrine Society
external identifiers
  • wos:000242581300050
  • scopus:33845473304
ISSN
1945-7197
DOI
10.1210/jc.2006-0679
language
English
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yes
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b38d7757-66ce-4915-97d6-17e06e2a9db3 (old id 683648)
date added to LUP
2007-12-28 21:22:45
date last changed
2019-08-04 04:33:21
@article{b38d7757-66ce-4915-97d6-17e06e2a9db3,
  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 congruent to 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, 5 alpha-androstane-3 alpha,17 beta-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 &lt; 0.001), dihydrotestosterone (P &lt; 0.05), and 5 alpha-androstane-3 alpha,17 beta- diol glucuronides (P &lt; 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.},
  author       = {Eriksson, A. L. and Lorentzon, M. and Mellstrom, D. and Vandenput, L. and Swanson, C. and Andersson, N. and Hammond, G. L. and Jakobsson, J. and Rane, A. and Orwoll, E. S. and Ljunggren, O. and Johnell, Olof and Labrie, F. and Windahl, S. H. and Ohlsson, C.},
  issn         = {1945-7197},
  language     = {eng},
  number       = {12},
  pages        = {5029--5037},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density},
  url          = {http://dx.doi.org/10.1210/jc.2006-0679},
  volume       = {91},
  year         = {2006},
}