Abstract
Summary
Animal models suggest a role for osteonectin/SPARC in determination of bone mass. We found haplotypes consisting of three single nucleotide polymorphisms (SNPs) in the 3′ untranslated region (UTR) of the osteonectin gene are associated with bone density in Caucasian men with idiopathic osteoporosis.
Introduction
Osteonectin is a matricellular protein regulating matrix assembly, osteoblast differentiation, and survival. Animal studies indicate that osteonectin is essential for normal bone mass. The 3′ UTR is a regulatory region controlling mRNA stability, trafficking, and translation, and we determined whether osteonectin 3′ UTR haplotypes could be associated with bone mass and/or idiopathic osteoporosis.
Methods
Single strand conformation polymorphism and allele-specific PCR analysis were used to assess alleles at osteonectin cDNA bases 1046, 1599, and 1970, using genomic DNA from middle-aged Caucasian men with idiopathic, low turnover osteoporosis (n = 56) and matched controls (n = 59). Bone density was measured by DXA at spine, hip and radius. Allele and haplotype frequencies were analyzed by Chi square analysis and Fisher’s exact test.
Results
Five common osteonectin 3′ UTR haplotypes were identified. The frequency of one haplotype (1046C-1599C-1970T) was higher in controls compared with patients, and this haplotype was also associated with higher bone densities at multiple sites in patients. In contrast, a second haplotype (1046C-1599G-1970T) was associated with lower bone densities in patients at multiple sites.
Conclusions
Osteonectin regulates skeletal remodeling and bone mass in animals, and haplotypes in the 3′ UTR of this gene are associated with bone density in Caucasian men with idiopathic osteoporosis.
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Acknowledgements
The authors gratefully acknowledge the expert technical assistance of Jonathan Shubert-Coleman, Ritu Bahl and Catherine Kessler. We thank Dr. Steve Mackey for his careful review of this manuscript and for helpful suggestions. We thank Dr. Mansoor Sarfarazi for his help in initiating the SNP analysis.
Funding
This work was supported by NIH grants AR44877 (AMD), DK31775 (DAG), NS27941 (DAG), AG20725 (ESK), as well as MO1RR06192 (University of Connecticut Health Center) and RR00645 (Columbia University Medical Center), and by the Donaghue Medical Research Foundation (AMD) and the National Osteoporosis Foundation/Mazess Research Award (ESK).
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Delany, A.M., McMahon, D.J., Powell, J.S. et al. Osteonectin/SPARC polymorphisms in Caucasian men with idiopathic osteoporosis. Osteoporos Int 19, 969–978 (2008). https://doi.org/10.1007/s00198-007-0523-9
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DOI: https://doi.org/10.1007/s00198-007-0523-9