1st Department of Internal Medicine, Semmelweis University, Korányi S u 2/a, Budapest H-1083, Hungary.
Eur J Endocrinol. 2010 Feb;162(2):423-31. doi: 10.1530/EJE-09-0617. Epub 2009 Nov 24.
Receptor activator of nuclear factor-kappaB ligand/osteoprotegerin (RANKL/OPG) signaling system plays a crucial role in the regulation of bone resorption. Polymorphic variations in the genes may have an influence on gene expression and bone metabolism. In the present study, we aimed to investigate the influence of RANKL/OPG allelic variations on the in vivo human gene expression of five genes, bone mineral density (BMD), and fracture incidence in Hungarian postmenopausal women.
Three hundred and sixty postmenopausal women (61.6+/-7.9 years) were genotyped. All together, five single nucleotide polymorphisms (SNPs) in the two genes have been investigated. In addition, bone samples from 17 examined subjects were acquired for gene expression studies. Bone densities and fracture data have also been collected.
All two SNPs in OPG gene and three SNPs in RANKL gene showed correlation with BMD. Haplotype analysis of these genes gave similar results. The 'CCT' haplotype of RANKL promoter region, which was associated with decreased BMD, exhibited a significantly upregulated expression of RANKL mRNA, while the other haplotypes of RANKL or OPG 15 genes did not. No correlation between genetic variations and fracture data was found.
We have demonstrated associations between RANKL and OPG haplotypes and BMD as well as between RANKL haplotypes and in vivo RANKL expression in a Hungarian postmenopausal population. Moreover, we have found a new RANKL haplotype associating with reduced BMD and increased in vivo RANKL expression in human bone tissue.
核因子-κB 受体激活物配体/骨保护素（RANKL/OPG）信号系统在调节骨吸收中起着至关重要的作用。基因中的多态性变异可能对基因表达和骨代谢产生影响。在本研究中，我们旨在研究 RANKL/OPG 等位基因变异对匈牙利绝经后妇女体内五个基因的基因表达、骨密度（BMD）和骨折发生率的影响。
对 360 名绝经后妇女（61.6+/-7.9 岁）进行基因分型。共研究了这两个基因中的 5 个单核苷酸多态性（SNP）。此外，还从 17 名被检查者中采集了骨样本来进行基因表达研究。还收集了骨密度和骨折数据。
OPG 基因中的两个 SNP 和 RANKL 基因中的三个 SNP 均与 BMD 相关。这些基因的单倍型分析也给出了相似的结果。与低 BMD 相关的 RANKL 启动子区域的“CCT”单倍型表现出 RANKL mRNA 的显著上调表达，而 RANKL 或 OPG 15 基因的其他单倍型则没有。遗传变异与骨折数据之间没有相关性。
我们已经证明了 RANKL 和 OPG 单倍型与 BMD 之间以及 RANKL 单倍型与匈牙利绝经后人群体内 RANKL 表达之间存在关联。此外，我们还发现了一种新的 RANKL 单倍型，它与人类骨组织中 BMD 降低和体内 RANKL 表达增加有关。
