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Polymorphisms in Genes Involved in the NF-kappa B Signalling Pathway Are Associated with Bone Mineral Density, Geometry and Turnover in Men

Roshandel, Delnaz; Thomson, Wendy; Pye, Stephen R.; Boonen, Steven; Borghs, Herman; Vanderschueren, Dirk; Huhtaniemi, Ilpo T.; Adams, Judith E.; Ward, Kate A. and Bartfai, Gyorgy, et al. (2011) In PLoS ONE 6(11).
Abstract
Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-kappa B cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods: Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r(2) >= 0.8) within MAP3K14 (+/-10 kb) were genotyped in 2359 men aged 40-79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray... (More)
Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-kappa B cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods: Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r(2) >= 0.8) within MAP3K14 (+/-10 kb) were genotyped in 2359 men aged 40-79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre. Results: We validated the associations between SNPs in GPR177 and BMDa previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMDa, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMDa, vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS. Conclusion: Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-kappa B signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health. (Less)
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11
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Public Library of Science
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  • scopus:81455133433
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1932-6203
DOI
10.1371/journal.pone.0028031
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English
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@article{588f10e0-0fae-4d41-9750-13fdbd8c9454,
  abstract     = {Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-kappa B cascade (GPR177 and MAP3K14) and bone mineral density (BMD) assessed at different skeletal sites, radial geometric parameters and bone turnover. Methods: Ten GPR177 SNPs previously associated with BMD with genome-wide significance and twelve tag SNPs (r(2) >= 0.8) within MAP3K14 (+/-10 kb) were genotyped in 2359 men aged 40-79 years recruited from 8 centres for participation in the European Male Aging Study (EMAS). Measurement of bone turnover markers (PINP and CTX-I) in the serum and quantitative ultrasound (QUS) at the calcaneus were performed in all centres. Dual energy X-ray absorptiometry (DXA), at the lumbar spine and hip, and peripheral quantitative computed tomography (pQCT), at the distal and midshaft radius, were performed in a subsample (2 centres). Linear regression was used to test for association between the SNPs and bone measures under an additive genetic model adjusting for study centre. Results: We validated the associations between SNPs in GPR177 and BMDa previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMDa, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMDa, vBMD, geometric parameters and CTX-I for SNPs in MAP3K14. None of the GPR177 and MAP3K14 SNPs were associated with calcaneal estimated BMD measured by QUS. Conclusion: Our findings suggest that SNPs in GPR177 and MAP3K14 involved in the NF-kappa B signalling pathway influence bone mineral density, geometry and turnover in a population-based cohort of middle aged and elderly men. This adds to the understanding of the role of genetic variation in this pathway in determining bone health.},
  author       = {Roshandel, Delnaz and Thomson, Wendy and Pye, Stephen R. and Boonen, Steven and Borghs, Herman and Vanderschueren, Dirk and Huhtaniemi, Ilpo T. and Adams, Judith E. and Ward, Kate A. 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 Wu, Frederick C. and Holliday, Kate L. and O'Neill, Terence W.},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Polymorphisms in Genes Involved in the NF-kappa B Signalling Pathway Are Associated with Bone Mineral Density, Geometry and Turnover in Men},
  url          = {http://dx.doi.org/10.1371/journal.pone.0028031},
  volume       = {6},
  year         = {2011},
}