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Association between repeat length of exon 1 CAG microsatellite in the androgen receptor and bone density in men is modulated by sex hormone levels
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Clinical pharmacogenetics and osteoporosis)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Metabolic Bone Diseases)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Clinical pharmacogenetics and osteoporosis)
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2008 (English)In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 82, no 6, 427-35 p.Article in journal (Refereed) Published
Abstract [en]

In this study we examined whether the androgen receptor (AR) gene CAG repeat polymorphism and serum androgen levels are associated with bone mineral density (BMD) and changes in BMD during 2-3 years in 229 healthy men 41-76 years old. Microsatellite analysis was performed on an automated sequencer. Indices of bioavailable testosterone (free testosterone [FT] and free androgen index) were calculated. BMD was measured using both dual-energy Xray absorptiometry and quantitative ultrasound. All participants completed a questionnaire regarding major possible osteoporosis risk factors. In linear regression analysis there was a modest positive association, which was independent of age and body mass index (BMI), between AR repeat length and BMD at all sites. Although this association was significant independent of BMI, analyses in the subgroup of obese men (BMI > 30) did not reach significance, while the effect was enhanced when analyzing only nonobese men (BMI < or = 30). There was no association between the AR gene polymorphism and rate of bone loss, FT, and BMD or testosterone and bone loss. Interestingly, the association between AR and BMD was modified by total testosterone. The lowest age- and BMI-adjusted average femoral neck BMD was found among men in the lowest tertile for both AR repeat length and FT, whereas men within the higher categories of these variables displayed the highest BMD. In conclusion, there is a positive association between the AR CAG repeat polymorphism and BMD, which is modified by androgen levels in healthy men.

Place, publisher, year, edition, pages
2008. Vol. 82, no 6, 427-35 p.
Keyword [en]
Androgen receptor, CAG microsatellite, Bone density, Sex hormone, Polymorphism
National Category
Medical and Health Sciences Surgery
Research subject
Orthopaedics
Identifiers
URN: urn:nbn:se:uu:diva-101162DOI: 10.1007/s00223-008-9128-3ISI: 000257869700003PubMedID: 18484228OAI: oai:DiVA.org:uu-101162DiVA: diva2:212004
Available from: 2009-04-20 Created: 2009-04-20 Last updated: 2017-12-13Bibliographically approved

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Michaelsson, KarlKindmark, Andreas

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