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- PMID: 21964949
- UKPMCID: 21964949
- DOI: 10.1007/s00223-011-9532-y
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Influence of Polymorphisms in the RANKL/RANK/OPG Signaling Pathway on Volumetric Bone Mineral Density and Bone Geometry at the Forearm in Men.
Roshandel, Delnaz; Holliday, Kate L; Pye, Stephen R; Ward, Kate A; Boonen, Steven; Vanderschueren, Dirk; Borghs, Herman; Huhtaniemi, Ilpo T; Adams, Judith E; Bartfai, Gyorgy; Casanueva, Felipe F; Finn, Joseph D; Forti, Gianni; Giwercman, Aleksander; Han, Thang S; Kula, Krzysztof; Lean, Michael E; Pendleton, Neil; Punab, Margus; Silman, Alan J; Wu, Frederick C; Thomson, Wendy; O'Neill, Terence W;
Calcified tissue international. 2011;.
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Full-text held externally
- PMID: 21964949
- UKPMCID: 21964949
- DOI: 10.1007/s00223-011-9532-y
Abstract
We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r (2) ≥ 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40-79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (β [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (β [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (β [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (β [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (β [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (β [95% CI] = -0.08 [-0.13 to -0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (β [95% CI] = -7.58 [-14.01 to -1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (β [95% CI] = 8.90 [0.92-16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.
Bibliographic metadata
- Roshandel, Delnaz
- Holliday, Kate L
- Pye, Stephen R
- Ward, Kate A
- Boonen, Steven
- Vanderschueren, Dirk
- Borghs, Herman
- Huhtaniemi, Ilpo T
- Adams, Judith E
- Bartfai, Gyorgy
- Casanueva, Felipe F
- Finn, Joseph D
- Forti, Gianni
- Giwercman, Aleksander
- Han, Thang S
- Kula, Krzysztof
- Lean, Michael E
- Pendleton, Neil
- Punab, Margus
- Silman, Alan J
- Wu, Frederick C
- Thomson, Wendy
- O'Neill, Terence W