rs9594759

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 examined 589 European men to determine whether SNPs in RANKL, RANK, and OPG genes influence volumetric bone mineral density (vBMD) and bone geometry at the radius. The authors identified 12 OPG SNPs associated with vBMD and geometric parameters (e.g., rs10505348 associated with total vBMD β=9.35, P=0.011; rs2073618 associated with cortical vBMD β=-4.30, P=0.015), three RANK SNPs associated with vBMD including rs12956925 associated with trabecular vBMD β=-7.58, P=0.021, and five RANK SNPs associated with geometric parameters including rs8083511 associated with cross-sectional area β=8.90, P=0.029. No significant associations were found with RANKL SNPs, suggesting genetic variation in OPG and RANK influences radius bone density and geometry in men.

This case-control study of 159 Ukrainian individuals (144 born macrosomic, 27 normosomic) investigates genetic associations with deciduous tooth eruption timing. The study identified associations between RANKL rs9594759 (multiplicative model, increased risk of delayed eruption) and IL10 rs1800896 (overdominant model, increased risk of delayed eruption). CYP19A1 rs2414096 G allele and ESR1 rs9340799 -351 A allele were found as risk factors for fetal macrosomia formation. RANKL and IL10 variants showed multidirectional modifying effects on tooth eruption timing in macrosomic individuals.

A replication study of 139 SNPs from three prior genome-wide association studies of bone mineral density in an independent sample of 1,000 unrelated US whites confirmed 38 SNPs (27% replication rate). Two SNPs achieved the most significant replication: rs3762397 in NR5A2 and rs3736228 in LRP5. Ten SNPs achieved combined p-values less than 3.6×10⁻⁴ across datasets, including rs3736228 (LRP5) with combined p=5.3×10⁻¹² for spinal BMD.