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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

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Abstract

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 X-ray 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 ≤ 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.

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Authors and Affiliations

  1. Department of Medical Sciences, University Hospital, MMS Ing 40 bv, Uppsala, SE-75185, Sweden

    Fredrik Stiger, Helena Brändström, Peter Gillberg, Håkan Melhus & Andreas Kindmark

  2. Department of Nutritional Epidemiology, The Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden

    Alicja Wolk

  3. Section of Orthopedics, Department of Surgical Sciences, University Hospital, Uppsala, Sweden

    Karl Michaelsson

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  1. Fredrik Stiger
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  2. Helena Brändström
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  4. Håkan Melhus
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Correspondence to Andreas Kindmark.

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Stiger, F., Brändström, H., Gillberg, P. et al. Association Between Repeat Length of Exon 1 CAG Microsatellite in the Androgen Receptor and Bone Density in Men is Modulated by Sex Hormone Levels. Calcif Tissue Int 82, 427–435 (2008). https://doi.org/10.1007/s00223-008-9128-3

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