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PLoS By Category | Recent PLoS Articles
Biophysics - Diabetes and Endocrinology - Physics - Radiology and Medical Imaging - Rheumatology

The ESR1 (6q25) Locus Is Associated with Calcaneal Ultrasound Parameters and Radial Volumetric Bone Mineral Density in European Men
Published: Thursday, July 07, 2011
Author: Kate L. Holliday et al.

by Kate L. Holliday, Stephen R. Pye, Wendy Thomson, Steven Boonen, Herman Borghs, Dirk Vanderschueren, Evelien Gielen, Ilpo T. Huhtaniemi, Judith E. Adams, Kate A. Ward, Gyorgy Bartfai, Felipe Casanueva, Joseph D. Finn, Gianni Forti, Aleksander Giwercman, Thang S. Han, Krzysztof Kula, Fernand Labrie, Michael E. J. Lean, Neil Pendleton, Margus Punab, Frederick C. W. Wu, Terence W. O'Neill, and the EMAS study group

Purpose

Genome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor a gene (ESR1), as a quantitative trait locus for areal bone mineral density (BMDa) of the hip and lumbar spine. The aim of this study was to determine the influence of this locus on other bone health outcomes; calcaneal ultrasound (QUS) parameters, radial peripheral quantitative computed tomography (pQCT) parameters and markers of bone turnover in a population sample of European men.

Methods

Eight single nucleotide polymorphisms (SNP) in the 6q25 locus were genotyped in men aged 40–79 years from 7 European countries, participating in the European Male Ageing Study (EMAS). The associations between SNPs and measured bone parameters were tested under an additive genetic model adjusting for centre using linear regression.

Results

2468 men, mean (SD) aged 59.9 (11.1) years had QUS measurements performed and bone turnover marker levels measured. A subset of 628 men had DXA and pQCT measurements. Multiple independent SNPs showed significant associations with BMD using all three measurement techniques. Most notably, rs1999805 was associated with a 0.10 SD (95%CI 0.05, 0.16; p?=?0.0001) lower estimated BMD at the calcaneus, a 0.14 SD (95%CI 0.05, 0.24; p?=?0.004) lower total hip BMDa, a 0.12 SD (95%CI 0.02, 0.23; p?=?0.026) lower lumbar spine BMDa and a 0.18 SD (95%CI 0.06, 0.29; p?=?0.003) lower trabecular BMD at the distal radius for each copy of the minor allele. There was no association with serum levels of bone turnover markers and a single SNP which was associated with cortical density was also associated with cortical BMC and thickness.

Conclusions

Our data replicate previous associations found between SNPs in the 6q25 locus and BMDa at the hip and extend these data to include associations with calcaneal ultrasound parameters and radial volumetric BMD.

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