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, 2006
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.
Sex Hormone-Binding Globulin
physiology
Aged
Mice
Hip
Adolescent
Transgenic
metabolism
Genetic
Promoter Regions (Genetics)
genetics
Adult
Genotype
Male
Microsatellite Repeats
Polymorphism
Bone Density
physiology
physiology
Mice
Animals
80 and over
Aged
blood
Androgens
Humans
analysis
Author
Anna-Lena Eriksson
University of Gothenburg
Mattias Lorentzon
University of Gothenburg
Dan Mellström
University of Gothenburg
Liesbeth Vandenput
University of Gothenburg
Charlotte Swanson
University of Gothenburg
Niklas Andersson
University of Gothenburg
Geoffrey L Hammond
Jenny Jakobsson
Anders Rane
Eric S Orwoll
Östen Ljunggren
Olof Johnell
Fernand Labrie
Sara H Windahl
University of Gothenburg
Claes Ohlsson
University of Gothenburg
Journal of Clinical Endocrinology and Metabolism
0021-972X (ISSN) 19457197 (eISSN)
Vol. 91 12 5029-37Subject Categories
MEDICAL AND HEALTH SCIENCES
DOI
10.1210/jc.2006-0679
PubMed
16926255