(WFRF:(Pye Stephen R.)) srt2:(2011)
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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 (author)
- Holliday, Kate L. (author)
- Pye, Stephen R. (author)
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- Ward, Kate A. (author)
- Boonen, Steven (author)
- Vanderschueren, Dirk (author)
- Borghs, Herman (author)
- Huhtaniemi, Ilpo T. (author)
- Adams, Judith E. (author)
- Bartfai, Gyorgy (author)
- Casanueva, Felipe F. (author)
- Finn, Joseph D. (author)
- Forti, Gianni (author)
- Han, Thang S. (author)
- Kula, Krzysztof (author)
- Lean, Michael E. (author)
- Pendleton, Neil (author)
- Punab, Margus (author)
- Silman, Alan J. (author)
- Wu, Frederick C. (author)
- Thomson, Wendy (author)
- O'Neill, Terence W. (author)
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- (creator_code:org_t)
- 2011-10-02
- 2011
- English.
- In: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 89:6, s. 446-455
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
Keyword
- Osteoporosis
- Genetic association
- Genetic polymorphism
- Male
- QCT
Publication and Content Type
- art (subject category)
- ref (subject category)
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- Borghs, Herman
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- Kula, Krzysztof
- Lean, Michael E.
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- Punab, Margus
- Silman, Alan J.
- Wu, Frederick C.
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- O'Neill, Terence ...
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