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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. and Bartfai, Gyorgy, et al. (2011) In Calcified Tissue International 89(6). p.446-455
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) a parts per thousand yen 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... (More)
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) a parts per thousand yen 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 (beta [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (beta [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (beta [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (beta [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (beta [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (beta [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 (beta [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 (beta [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. (Less)
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keywords
Osteoporosis, Genetic association, Genetic polymorphism, Male, QCT
in
Calcified Tissue International
volume
89
issue
6
pages
446 - 455
publisher
Springer
external identifiers
  • wos:000297117600004
  • scopus:82455192283
ISSN
1432-0827
DOI
10.1007/s00223-011-9532-y
language
English
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yes
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915b18b2-fe38-40b5-800a-db430d065837 (old id 2243172)
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2012-01-02 07:55:18
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@article{915b18b2-fe38-40b5-800a-db430d065837,
  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) a parts per thousand yen 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 (beta [95% CI] = 9.35 [2.12-16.58], P = 0.011), cortical vBMD (beta [95% CI] = 5.62 [2.10-9.14], P = 0.002), cortical thickness (beta [95% CI] = 0.08 [0.03-0.13], P = 0.002), and medullary area (beta [95% CI] = -2.90 [-4.94 to -0.86], P = 0.005) and rs2073618 associated with cortical vBMD (beta [95% CI] = -4.30 [-7.78 to -0.82], P = 0.015) and cortical thickness (beta [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 (beta [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 (beta [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.},
  author       = {Roshandel, Delnaz and Holliday, Kate L. and Pye, Stephen R. and Ward, Kate A. and Boonen, Steven and Vanderschueren, Dirk and Borghs, Herman and Huhtaniemi, Ilpo T. and Adams, Judith E. and Bartfai, Gyorgy and Casanueva, Felipe F. and Finn, Joseph D. and Forti, Gianni and Giwercman, Aleksander and Han, Thang S. and Kula, Krzysztof and Lean, Michael E. and Pendleton, Neil and Punab, Margus and Silman, Alan J. and Wu, Frederick C. and Thomson, Wendy and O'Neill, Terence W.},
  issn         = {1432-0827},
  keyword      = {Osteoporosis,Genetic association,Genetic polymorphism,Male,QCT},
  language     = {eng},
  number       = {6},
  pages        = {446--455},
  publisher    = {Springer},
  series       = {Calcified Tissue International},
  title        = {Influence of Polymorphisms in the RANKL/RANK/OPG Signaling Pathway on Volumetric Bone Mineral Density and Bone Geometry at the Forearm in Men},
  url          = {http://dx.doi.org/10.1007/s00223-011-9532-y},
  volume       = {89},
  year         = {2011},
}