rs7239261

A cross-sectional study of 881 postmenopausal Chinese women examined associations between 22 SNPs in the RANKL/RANK/OPG pathway genes (TNFSF11, TNFRSF11A, TNFRSF11B) and bone mineral density (BMD). Two TNFSF11 SNPs (rs2277439 and rs2324851; p=0.014, 0.013) and one TNFRSF11A SNP (rs7239261; p=0.047) were significantly associated with femoral neck BMD. A haplotype in TNFSF11 was a genetic risk factor for lower femoral neck BMD (beta=-0.1473; p=0.011), while another was protective for lumbar spine BMD (beta=0.3923; p=0.049).

This association study identifies genetic variants in the TNFRSF11A gene (encoding RANK) associated with susceptibility to sporadic Paget's disease of bone (PDB) in three European populations. Meta-analysis across Belgian, Dutch, and British cohorts shows rs1805034 (A192V, p=1.27×10⁻⁸, OR=1.627) and rs35211496 (H141Y, p=.002, OR=1.410) are significantly associated with PDB, with strongest effects observed in females. Haplotype analysis in Belgian females identified risk haplotypes CGACGAA and AAAGGG with ORs of 2.808 and 3.462 respectively, though functional studies did not identify a definitive causative variant.