VDR, RANKL and OPG polymorphisms as possible predisposing cofactors of postmenopausal osteoporosis: explorative study in Italian population

Abstract

Postmenopausal osteoporosis (PO) has a strong genetic component. Presently, the published evidence on the association between the main single-nucleotide polymorphisms (SNPs) of the receptor activator of nuclear factor-kb ligand (RANKL), osteoprotegerin (OPG) and vitamin D receptor (VDR) and bone mass density (BMD) are scarce, mostly considering Italian population. This study sought to determine whether OPG (rs2073618), RANKL (rs9525641) and the VDR (rs2228570) SNPs were associated with BMD in a sample of 139 North-Italian postmenopausal women. The allelic distribution of rs9525641 in women with PO or osteopenia (OP + OPE group) differed from controls (p < 0.05), suggesting that this allele might confer a greater susceptibility to bone resorption. Concerning rs2228570, CC genotype was associated with OP + OPE women, with a worst total hip BMD. Notably, the combined genotype RANK (CT)–VDR (TT) was significantly associated to spine BMD (p < 0.05). In conclusion, this pilot study showed that rs9525641 and rs2228570 polymorphisms might contribute, separately or in combination, in determining BMD phenotype in selected postmenopausal populations.

Chinese abstract

绝经后骨质疏松症（PO）很大程度上受遗传因素的影响。目前意大利关于细胞核因子κB受体活化因子配基（RANKL）, 骨保护素（OPG）、维生素D受体（VDR）主要单核苷酸多态性（SNP）与骨密度（BMD）关系的相关研究很少。本研究以139例北意大利绝经后女性为研究对象, 旨在确定OPG（rs2073618）, RANKL（rs9525641）和VDR（rs2228570）SNPs是否与BMD相关。rs9525641基因型在PO或骨质减少症患者中（OP + OPE组）的等位基因分布频率与对照组有差异（p < 0.05）, 表明该等位基因可能具有较高的骨吸收易感性。rs2228570, CC基因型多态性与OP + OPE患者有相关性,这些患者全髋BMD最低。值得注意的是, 组合基因型RANK（CT）-VDR（TT）多态性与脊柱BMD显著相关（p < 0.05）。综上所述, 这项试验研究表明在绝经后人群中rs9525641和rs2228570多态性可能会以单独或组合起作用的形式对不同部位BMD造成影响。

Keywords:

• Bone mass density
• OPG
• osteoporosis
• Vitamin D receptor
• RANKL

Acknowledgements

The authors thank Monica Squerzanti for her meaningful contributions in data collection and processing.

Declaration of interest

The authors declare no conflict of interest.

Supplementary material available online