Polymorphisms in genes involved in the NF-κb signalling pathway are associated with bone mineral density, geometry and turnover in men

Delnaz Roshandel, Wendy Thomson, Stephen R. Pye, Steven Boonen, Herman Borghs, Dirk Vanderschueren, Ilpo T. Huhtaniemi, Judith E. Adams, Kate A. Ward, G. Bártfai, Felipe F. Casanueva, Joseph D. Finn, Gianni Forti, Aleksander Giwercman, Thang S. Han, Krzysztof Kula, Michael E. Lean, Neil Pendleton, Margus Punab, Frederick C. WuKate L. Holliday, Terence W. O'Neill, EMAS Study Group the EMAS Study Group

Research output: Contribution to journalArticle

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Abstract

Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-κB 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 BMD a previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMD a, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMD a, 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-κB 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.

Original languageEnglish
Article numbere28031
JournalPLoS One
Volume6
Issue number11
DOIs
Publication statusPublished - Nov 21 2011

Fingerprint

Bone Remodeling
bone density
Polymorphism
Bone Density
single nucleotide polymorphism
Single Nucleotide Polymorphism
Minerals
Bone
Genes
genetic polymorphism
Geometry
Nucleotides
genes
bones
radius (bone)
hips
middle-aged adults
Pelvic Bones
lumbar spine
Bone and Bones

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Roshandel, D., Thomson, W., Pye, S. R., Boonen, S., Borghs, H., Vanderschueren, D., ... the EMAS Study Group, EMAS. S. G. (2011). Polymorphisms in genes involved in the NF-κb signalling pathway are associated with bone mineral density, geometry and turnover in men. PLoS One, 6(11), [e28031]. https://doi.org/10.1371/journal.pone.0028031

Polymorphisms in genes involved in the NF-κb 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.; Bártfai, G.; Casanueva, Felipe F.; Finn, Joseph D.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Kula, Krzysztof; Lean, Michael E.; Pendleton, Neil; Punab, Margus; Wu, Frederick C.; Holliday, Kate L.; O'Neill, Terence W.; the EMAS Study Group, EMAS Study Group.

In: PLoS One, Vol. 6, No. 11, e28031, 21.11.2011.

Research output: Contribution to journalArticle

Roshandel, D, Thomson, W, Pye, SR, Boonen, S, Borghs, H, Vanderschueren, D, Huhtaniemi, IT, Adams, JE, Ward, KA, Bártfai, G, Casanueva, FF, Finn, JD, Forti, G, Giwercman, A, Han, TS, Kula, K, Lean, ME, Pendleton, N, Punab, M, Wu, FC, Holliday, KL, O'Neill, TW & the EMAS Study Group, EMASSG 2011, 'Polymorphisms in genes involved in the NF-κb signalling pathway are associated with bone mineral density, geometry and turnover in men', PLoS One, vol. 6, no. 11, e28031. https://doi.org/10.1371/journal.pone.0028031
Roshandel, Delnaz ; Thomson, Wendy ; Pye, Stephen R. ; Boonen, Steven ; Borghs, Herman ; Vanderschueren, Dirk ; Huhtaniemi, Ilpo T. ; Adams, Judith E. ; Ward, Kate A. ; Bártfai, G. ; Casanueva, Felipe F. ; Finn, Joseph D. ; Forti, Gianni ; Giwercman, Aleksander ; Han, Thang S. ; Kula, Krzysztof ; Lean, Michael E. ; Pendleton, Neil ; Punab, Margus ; Wu, Frederick C. ; Holliday, Kate L. ; O'Neill, Terence W. ; the EMAS Study Group, EMAS Study Group. / Polymorphisms in genes involved in the NF-κb signalling pathway are associated with bone mineral density, geometry and turnover in men. In: PLoS One. 2011 ; Vol. 6, No. 11.
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abstract = "Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-κB 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 BMD a previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMD a, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMD a, 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-κB 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.",
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T1 - Polymorphisms in genes involved in the NF-κb signalling pathway are associated with bone mineral density, geometry and turnover in men

AU - Roshandel, Delnaz

AU - Thomson, Wendy

AU - Pye, Stephen R.

AU - Boonen, Steven

AU - Borghs, Herman

AU - Vanderschueren, Dirk

AU - Huhtaniemi, Ilpo T.

AU - Adams, Judith E.

AU - Ward, Kate A.

AU - Bártfai, G.

AU - Casanueva, Felipe F.

AU - Finn, Joseph D.

AU - Forti, Gianni

AU - Giwercman, Aleksander

AU - Han, Thang S.

AU - Kula, Krzysztof

AU - Lean, Michael E.

AU - Pendleton, Neil

AU - Punab, Margus

AU - Wu, Frederick C.

AU - Holliday, Kate L.

AU - O'Neill, Terence W.

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N2 - Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-κB 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 BMD a previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMD a, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMD a, 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-κB 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.

AB - Introduction: In this study, we aimed to investigate the association between single nucleotide polymorphisms (SNPs) within two genes involved in the NF-κB 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 BMD a previously reported and also observed evidence of pleiotrophic effects on density and geometry. Rs2772300 in GPR177 was associated with increased total hip and LS BMD a, increased total and cortical vBMD at the radius and increased cortical area, thickness and stress strain index. We also found evidence of association with BMD a, 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-κB 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.

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