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Genetic Variation in the RANKL/RANK/OPG Signaling Pathway Is Associated With Bone Turnover and Bone Mineral Density in Men

Roshandel, Delnaz; Holliday, Kate L.; Pye, Stephen R.; Boonen, Steven; Borghs, Herman; Vanderschueren, Dirk; Huhtaniemi, Ilpo T.; Adams, Judith E.; Ward, Kate A. and Bartfai, Gyorgy, et al. (2010) In Journal of Bone and Mineral Research 25(8). p.1830-1838
Abstract
The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r(2) >= 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was... (More)
The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r(2) >= 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMDa) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (beta = 1.83, p = .004) and CTX-I (beta = 17.59, p = 4.74 x 10(-4)), and lower lumbar spine BMDa (beta = -0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (beta = -1.84, p = .003) and CTX-I (beta = -27.02, p = 6.06 x 10(-8)) and higher ultrasound BMD at the calcaneus (beta = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. (c) 2010 American Society for Bone and Mineral Research. (Less)
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BONE TURNOVER MARKERS, SNPS, OSTEOPOROSIS, ASSOCIATION, BONE, DENSITOMETRY
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Journal of Bone and Mineral Research
volume
25
issue
8
pages
1830 - 1838
publisher
AMBMR
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  • wos:000281325000013
  • scopus:77955740567
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1523-4681
DOI
10.1002/jbmr.78
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English
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76d89309-9800-455e-9808-a901b2177489 (old id 1673098)
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@article{76d89309-9800-455e-9808-a901b2177489,
  abstract     = {The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r(2) >= 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMDa) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (beta = 1.83, p = .004) and CTX-I (beta = 17.59, p = 4.74 x 10(-4)), and lower lumbar spine BMDa (beta = -0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (beta = -1.84, p = .003) and CTX-I (beta = -27.02, p = 6.06 x 10(-8)) and higher ultrasound BMD at the calcaneus (beta = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. (c) 2010 American Society for Bone and Mineral Research.},
  author       = {Roshandel, Delnaz and Holliday, Kate L. 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 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         = {1523-4681},
  keyword      = {BONE TURNOVER MARKERS,SNPS,OSTEOPOROSIS,ASSOCIATION,BONE,DENSITOMETRY},
  language     = {eng},
  number       = {8},
  pages        = {1830--1838},
  publisher    = {AMBMR},
  series       = {Journal of Bone and Mineral Research},
  title        = {Genetic Variation in the RANKL/RANK/OPG Signaling Pathway Is Associated With Bone Turnover and Bone Mineral Density in Men},
  url          = {http://dx.doi.org/10.1002/jbmr.78},
  volume       = {25},
  year         = {2010},
}