Department of Endocrinology, University of Ioannina, Ioannina, Greece.
Maturitas. 2011 Oct;70(2):188-93. doi: 10.1016/j.maturitas.2011.07.016. Epub 2011 Aug 15.
Wnt signaling through low-density lipoprotein receptor-related protein 5 (LRP5) is an important determinant of bone mass regulation.
To explore the influence of two LRP5 single nucleotide polymorphisms (SNPs) A1330V and V667M on bone mineral density (BMD) and serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and bone metabolic markers in a Greek female population.
Two hundred and nine postmenopausal and twelve perimenopausal women aged 40-63 years were enrolled. All participants underwent spinal BMD evaluation. Genotyping of A1330V and V667M polymorphisms was performed by real-time polymerase chain reaction. Levels of OPG, soluble RANKL (sRANKL) and bone metabolic markers were measured.
As regards A1330V SNP, women carrying CT/TT genotypes had lower spinal BMD than women with CC (p<0.0001). Regarding V667M SNP, spinal BMD was lower in women with GA/AA than in women with GG genotypes (p<0.0001). These differences remained significant after adjustment for age, years since menopause and body mass index. The A1330V and V667M polymorphisms were in strong linkage disequilibrium. A significant interaction between A1330V and V667M SNPs on spinal BMD was revealed. The haplotype with both risk alleles of the two SNPs (AT) conferred more risk for low BMD than the haplotypes with one risk allele (GT or AC) or the haplotype-reference (GC) (p=0.046, p=0.045, and p=0.010, respectively). No effect was observed on circulating OPG, sRANKL levels and bone metabolic markers.
These findings demonstrate that the A1330V and V667M polymorphisms are associated with low BMD in peri- and postmenopausal Greek women.
Wnt 信号通过低密度脂蛋白受体相关蛋白 5（LRP5）是调节骨量的重要决定因素。
探索 LRP5 两个单核苷酸多态性（SNP）A1330V 和 V667M 对希腊女性人群骨密度（BMD）和血清骨保护素（OPG）、核因子-κB 受体激活剂配体（RANKL）和骨代谢标志物水平的影响。
招募了 209 名绝经后和 12 名围绝经期年龄在 40-63 岁的女性。所有参与者均接受了脊柱 BMD 评估。通过实时聚合酶链反应对 A1330V 和 V667M 多态性进行基因分型。测量 OPG、可溶性 RANKL（sRANKL）和骨代谢标志物的水平。
就 A1330V SNP 而言，携带 CT/TT 基因型的女性脊柱 BMD 低于 CC 基因型的女性（p<0.0001）。对于 V667M SNP，GA/AA 基因型的女性脊柱 BMD 低于 GG 基因型的女性（p<0.0001）。这些差异在调整年龄、绝经年限和体重指数后仍然显著。A1330V 和 V667M 多态性之间存在强烈的连锁不平衡。揭示了 A1330V 和 V667M SNP 对脊柱 BMD 的显著相互作用。与携带一个风险等位基因的两种 SNP（GT 或 AC）的单倍型或与参考单倍型（GC）相比，两种 SNP 的风险等位基因（AT）的单倍型赋予了更低 BMD 的更多风险（p=0.046，p=0.045，p=0.010）。对循环 OPG、sRANKL 水平和骨代谢标志物没有影响。
这些发现表明，A1330V 和 V667M 多态性与希腊绝经前和绝经后女性的低 BMD 相关。
