Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA.
J Bone Miner Res. 2010 Feb;25(2):320-9. doi: 10.1359/jbmr.090726.
Poor femoral neck bone geometry at the femur is an important risk factor for hip fracture. We conducted a genome-wide association study (GWAS) of femoral neck bone geometry, examining approximately 379,000 eligible single-nucleotide polymorphisms (SNPs) in 1000 Caucasians. A common genetic variant, rs7430431 in the receptor transporting protein 3 (RTP3) gene, was identified in strong association with the buckling ratio (BR, P = 1.6 x 10(-7)), an index of bone structural instability, and with femoral cortical thickness (CT, P = 1.9 x 10(-6)). The RTP3 gene is located in 3p21.31, a region that we found to be linked with CT (LOD = 2.19, P = 6.0 x 10(-4)) in 3998 individuals from 434 pedigrees. The replication analyses in 1488 independent Caucasians and 2118 Chinese confirmed the association of rs7430431 to BR and CT (combined P = 7.0 x 10(-3) for BR and P = 1.4 x 10(-2) for CT). In addition, 350 hip fracture patients and 350 healthy control individuals were genotyped to assess the association of the RTP3 gene with the risk of hip fracture. Significant association between a nearby common SNP, rs10514713 of the RTP3 gene, and hip fracture (P = 1.0 x 10(-3)) was found. Our observations suggest that RTP3 may be a novel candidate gene for femoral neck bone geometry.
股骨颈骨几何形状较差是髋部骨折的一个重要危险因素。我们对股骨颈骨几何形状进行了全基因组关联研究（GWAS），在 1000 名白种人中检查了大约 379,000 个合格的单核苷酸多态性（SNP）。受体转运蛋白 3（RTP3）基因中的一个常见遗传变异体 rs7430431 与骨结构不稳定指数（BR）强烈相关（P=1.6x10(-7)），与股骨皮质厚度（CT）相关（P=1.9x10(-6)）。RTP3 基因位于 3p21.31 上，我们发现该区域与 CT 相关（LOD=2.19，P=6.0x10(-4)），在来自 434 个家系的 3998 个人中。在 1488 名独立的白种人和 2118 名中国人的复制分析中，rs7430431 与 BR 和 CT 的相关性得到了证实（BR 的综合 P=7.0x10(-3)，CT 的 P=1.4x10(-2)）。此外，对 350 名髋部骨折患者和 350 名健康对照个体进行基因分型，以评估 RTP3 基因与髋部骨折风险的相关性。发现 RTP3 基因附近常见 SNP rs10514713 与髋部骨折显著相关（P=1.0x10(-3))。我们的观察结果表明，RTP3 可能是股骨颈骨几何形状的一个新的候选基因。
