OPG and RANK polymorphisms are both associated with cortical bone mineral density: Findings from a metaanalysis of the avon longitudinal study of parents and children and Gothenburg osteoporosis and obesity determinants cohorts

Paternoster, L., Ohlsson, C., Sayers, A., Vandenput, L., Lorentzon, M., Evans, D. M. and Tobias, J. H. (2010) OPG and RANK polymorphisms are both associated with cortical bone mineral density: Findings from a metaanalysis of the avon longitudinal study of parents and children and Gothenburg osteoporosis and obesity determinants cohorts. Journal of Clinical Endocrinology and Metabolism, 95 8: 3940-3948. doi:10.1210/jc.2010-0025


Author Paternoster, L.
Ohlsson, C.
Sayers, A.
Vandenput, L.
Lorentzon, M.
Evans, D. M.
Tobias, J. H.
Title OPG and RANK polymorphisms are both associated with cortical bone mineral density: Findings from a metaanalysis of the avon longitudinal study of parents and children and Gothenburg osteoporosis and obesity determinants cohorts
Formatted title
OPG and RANK polymorphisms are both associated with cortical bone mineral density: Findings from a metaanalysis of the avon longitudinal study of parents and children and Gothenburg osteoporosis and obesity determinants cohorts
Journal name Journal of Clinical Endocrinology and Metabolism   Check publisher's open access policy
ISSN 0021-972X
1945-7197
Publication date 2010
Sub-type Article (original research)
DOI 10.1210/jc.2010-0025
Open Access Status
Volume 95
Issue 8
Start page 3940
End page 3948
Total pages 9
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Language eng
Formatted abstract
Context: Several single-nucleotide polymorphisms (SNPs) have been reliably associated with areal bone mineral density (aBMD) in genome-wide association studies of mostly older subjects.

Objective: We aimed to test those SNPs for an association with peripheral quantitative computed tomography (pQCT) bone measures in two young cohorts.

Design and Study Participants: We genotyped nine SNPs from the most promising aBMD candidates in a cohort of 15-yr-olds [in the Avon Longitudinal Study of Parents and Children (ALSPAC)] and carried out association analysis with several tibial pQCT measures to determine whether these candidates were important during adolescent growth and which particular skeletal parameters each of the candidates were acting upon. We also carried out a metaanalysis of the SNPs for association with cortical bone mineral density (BMD C) in ALSPAC and a similar male-only study (Gothenburg Osteoporosis and Obesity Determinants).

Results: In the ALSPAC cohort, we found a significant association between RANK SNP (rs3018362) and BMD C but not any of the other pQCT bone measures. In the metaanalysis, we found the OPG SNP (rs4355801) and the RANK SNP (rs3018362) to be significantly associated with BMD C. We also found suggestive evidence of an association between the MARK3 SNP (rs2010281) and BMD C but with a direction of effect opposite to that previously reported.

Conclusion: The association of genes from the RANK/RANKL/OPG pathway and BMD C provides new insight into how this system might affect the skeleton, confirming it to be associated with volumetric cortical bone density but observing no relationship with bone size. Copyright 
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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