Association of the OSCAR promoter polymorphism with BMD in postmenopausal women

Introduction: BMD is the major factor for determining bone strength and osteoporotic fracture risk and is determined by both environmental and multiple genetic factors. The osteoclast-associated receptor (OSCAR) plays a critical role in osteoclast differentiation and thus is an Important candidate gene for the modulation of BMD. Materials and Methods: Through direct sequencing in 24 Korean individuals, 10 sequence variants were identified: 2 in the 5' flanking region, 7 in the exons (including 6 nonsynonymous single-nucleotide polymorphisms [SNPs]), and 1 in an intron. Five of these polymorphisms were selected for larger-scale genotyping in postmenopausal women (n = 560). Areal BMD (g/cm(2)) of the anterior-posterior lumbar spine and the nondominant proximal femur was measured using DXA (Lunar Expert XL and Hologic QDR 4500-A). Lateral thoracolumbar radiographs were obtained in all subjects. Results: Using multiple regression analysis and controlling for age, years since menopause, height, weight, and evaluation machine as covariates, the rare allele (G allele) of OSCAR-2322A > G showed significant association with lower BMD at various bone sites in postmenopausal women. Conclusion: These findings suggest that the promoter variant in OSCAR gene (OSCAR-2322A > G) might be one of genetic determinants of BMD in postmenopausal women.