Osteonectin/SPARC polymorphisms in Caucasian men with idiopathic osteoporosis

• Published in: Osteoporosis international 2008-07, Vol.19 (7), p.969-978
• Main Authors: Delany, A. M., McMahon, D. J., Powell, J. S., Greenberg, D. A., Kurland, E. S.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Bone density; Bone Density - genetics; Diseases of the osteoarticular system; Endocrinology; Gene Frequency - genetics; Genetic Predisposition to Disease - genetics; Genotype & phenotype; Haplotypes - genetics; Hip - diagnostic imaging; Humans; Lumbar Vertebrae - diagnostic imaging; Male; Medical sciences; Medicine; Medicine & Public Health; Men; Middle Aged; Original Article; Orthopedics; Osteonectin - genetics; Osteoporosis; Osteoporosis - genetics; Osteoporosis. Osteomalacia. Paget disease; Polymerase Chain Reaction; Polymorphism; Polymorphism, Single Nucleotide - genetics; Radiography; Radius - diagnostic imaging; Rheumatology; White people
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-007-0523-9

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.