Abstract
PurposeGenome-wide association studies (GWAS) have identified 6q25, which incorporates the oestrogen receptor α 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.MethodsEight 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.Results2468 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.ConclusionsOur 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.
Highlights
Oestrogens have positive effects on the development and maintenance of the skeleton
The majority of previous work has focussed on oestrogens and the female skeleton, but more recent evidence suggests that oestrogens are required for the maintenance of bone health in men [1,2,3,4,5,6,7,8,9]
We examined if 6q25 was associated with bone health as measured by Quantitative ultrasound (QUS) at the calcaneus, peripheral quantitative computed tomography (pQCT) at the radius and serum markers of bone turnover
Summary
Oestrogens have positive effects on the development and maintenance of the skeleton. These effects include the regulation of bone turnover, acquisition of peak bone mass and inhibition of bone loss. The effects are mediated through binding to specific oestrogen receptors (ER), which belong to the nuclear hormone receptor superfamily and are expressed in a number of cell types including osteoblasts, osteoclasts and bone marrow stromal cells [10,11]. Two functional oestrogen receptors have been identified so far, ERa and ERb. ERa appears to be the major receptor, having a prominent effect on bone metabolism [12]
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