Common Variants in OPG Confer Risk to Bone Mineral Density Variation and Osteoporosis Fractures

Although many common variants have been identified for bone mineral density (BMD) and osteoporosis fractures, all the identified risk variants could only explain a small portion of heritability of BMD and osteoporosis fractures. OPG belongs to the tumor necrosis factor receptor superfamily, which plays a crucial role in bone remodeling and is thus a promising candidate gene of osteoporosis. Several studies have explored the association of OPG variants with BMD or osteoporosis fractures, however, the results remain inconsistent among different populations. In the study, we first assessed the relationship between OPG variants and BMD or osteoporosis fractures in our sample size (227 subjects with postmenopausal osteoporosis and 189 controls), and then performed a systematic meta-analysis. Among the nine SNPs genotyped, rs6469804 and rs2073618 showed significant associations with both BMD and osteoporotic fractures, while rs3102735 was only associated with BMD in our samples (P < 0.05). For meta-analyses, data for a total of 12 SNPs were pooled (4725 patients and 37804 controls), and five SNPs, including rs6993813, rs6469804, rs3134070, rs2073618 and rs3102734, showed association with osteoporosis fractures (P < 0.05). On light of the above analysis, we believe that OPG is one promising susceptibility gene of BMD or osteoporotic fractures.