Tu P, Duan P, Zhang R-S, Xu D-B, Wang Y, Wu H-P, Liu Y-H, Si L
Department of Endocrinology and Metabolism, The Third Hospital of Nanchang, Nanchang Key Laboratory of Diabetes, Nanchang, Jiangxi Province, 330009, China,
Osteoporos Int. 2015 Jan;26(1):179-85. doi: 10.1007/s00198-014-2854-7. Epub 2014 Aug 20.
Association between 22 single nucleotide polymorphisms (SNPs) in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in 881 post-menopausal women. Our results suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women.
The aim of this study was to assess the relationship of polymorphisms in the TNFSF11, TNFRSF11A, and TNFRSF11B genes in the RANKL/RANK/OPG pathway with bone mineral density (BMD) in a cohort of Chinese post-menopausal women.
A cross-sectional study was conducted in 881 post-menopausal women aged 50-89 years. All participants underwent lumbar spinal (LS) and femoral neck (FN) BMD evaluation by dual-energy X-ray absorptiometry. Twenty-two TNFSF11, TNFRSF11A, and TNFRSF11B SNPs were genotyped. We tested whether a single SNP or a haplotype was associated with BMD variations.
Two SNPs in the TNFSF11 gene (rs2277439 and rs2324851) and one in the TNFRSF11A gene (rs7239261) were found to be significantly associated with FN BMD (p = 0.014, 0.013, and 0.047, respectively). Haplotype TGACGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was a genetic risk factor toward a lower FN BMD (beta = -0.1473; p = 0.01126). In contrary, haplotype TAGCGT of TNFSF11 rs9525641-rs2277439-rs2324851-rs2875459-rs2200287-rs9533166 was genetic protective factor for LS BMD (beta = 0.3923; p = 0.04917).
Our findings suggest that TNFSF11 and TNFRSF11A, but not TNFRSF11B, genetic polymorphisms influence BMD mainly in the femoral neck in post-menopausal Chinese women. This contributes to the understanding of the role of genetic variation in this pathway in determining bone health.
RANKL/RANK/OPG通路中TNFSF11、TNFRSF11A和TNFRSF11B基因的22个单核苷酸多态性（SNP）与881名绝经后女性骨密度（BMD）之间的关联。我们的结果表明，TNFSF11和TNFRSF11A基因多态性而非TNFRSF11B基因多态性主要影响绝经后中国女性股骨颈的骨密度。
本研究旨在评估RANKL/RANK/OPG通路中TNFSF11、TNFRSF11A和TNFRSF11B基因多态性与中国绝经后女性队列骨密度（BMD）之间的关系。
对881名年龄在50 - 89岁的绝经后女性进行了横断面研究。所有参与者均通过双能X线吸收法进行腰椎（LS）和股骨颈（FN）骨密度评估。对22个TNFSF11、TNFRSF11A和TNFRSF11B单核苷酸多态性进行基因分型。我们测试了单个单核苷酸多态性或单倍型是否与骨密度变化相关。
发现TNFSF11基因中的两个单核苷酸多态性（rs2277439和rs2324851）以及TNFRSF11A基因中的一个单核苷酸多态性（rs7239261）与股骨颈骨密度显著相关（p分别为0.014、0.013和0.047）。TNFSF11 rs9525641 - rs2277439 - rs2324851 - rs2875459 - rs2200287 - rs9533166的单倍型TGACGT是股骨颈骨密度降低的遗传危险因素（β = -0.1473；p = 0.01126）。相反，TNFSF11 rs9525641 - rs2277439 - rs2324851 - rs2875459 - rs2200287 - rs9533166的单倍型TAGCGT是腰椎骨密度的遗传保护因素（β = 0.3923；p = 0.04917）。
我们的研究结果表明，TNFSF11和TNFRSF11A基因多态性而非TNFRSF11B基因多态性主要影响绝经后中国女性股骨颈的骨密度。这有助于理解该通路中基因变异在决定骨骼健康中的作用。
