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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.

Journal article
Authors Anna-Lena Eriksson
Mattias Lorentzon
Dan Mellström
Liesbeth Vandenput
Charlotte Swanson
Niklas Andersson
Geoffrey L Hammond
Jenny Jakobsson
Anders Rane
Eric S Orwoll
Östen Ljunggren
Olof Johnell
Fernand Labrie
Sara H Windahl
Claes Ohlsson
Published in The Journal of clinical endocrinology and metabolism
Volume 91
Issue 12
Pages 5029-37
ISSN 0021-972X
Publication year 2006
Published at Institute of Medicine, School of Public Health and Community Medicine
Institute of Medicine, Department of Internal Medicine
Pages 5029-37
Language en
Links dx.doi.org/10.1210/jc.2006-0679
Keywords Adolescent, Adult, Aged, Aged, 80 and over, Androgens, blood, metabolism, Animals, Bone Density, physiology, Genotype, Hip, physiology, Humans, Male, Mice, Mice, Transgenic, Microsatellite Repeats, physiology, Polymorphism, Genetic, Promoter Regions (Genetics), Sex Hormone-Binding Globulin, analysis, genetics
Subject categories Medical and Health Sciences

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 with 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, 5alpha-androstane-3alpha,17beta-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 5alpha-androstane-3alpha,17beta-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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