LRP4 association to bone properties and fracture and interaction with genes in the Wnt- and BMP signaling pathways
LRP4 association to bone properties and fracture and interaction with genes in the Wnt- and BMP signaling pathways
复制标题
DOI：
10.1016/j.bone.2011.05.018
复制
发表时间：
2011-09-01
期刊：
影响因子：
4.1
通讯作者：
Akesson, Kristina
中科院分区：
文献类型：
--
作者：
Kumar, Jitender;Swanberg, Maria;Akesson, Kristina
骨质疏松症是绝经后妇女常见的复杂疾病，导致骨微结构的改变和骨折的风险增加。低密度脂蛋白受体相关蛋白（LRP）基因家族的成员通过Wnt/ β -连环蛋白（Wnt）途径调节骨的发育和生理，而Wnt/ β -连环蛋白（Wnt）途径又与骨形态发生蛋白（BMP）途径交叉对话。在两个瑞典女性队列：OPRA （n = 1002，年龄75岁）和PEAK-25 （n = 1005，年龄25岁）中，分析了来自Wnt通路基因（LRP4; LRP5； G蛋白偶联受体177，GPR177）的11个单核苷酸多态性（snp）与骨密度（BMD）、骨质流失率、髋关节几何形状、定量超声和骨折的关系。此外，还分析了LRP4与LRP5、GPR177和BMP2的相互作用。在PEAK-25队列中，LRP4 （rs6485702）与较高的全身（TB）和腰椎（LS）骨密度相关（分别为p = 0.006和0.005），并与LRP5 （p = 0.007）和BMP2 （p = 0.004）相互作用。在该队列中，LRP4与LRP5在股骨颈（FN）和LS骨密度方面也表现出显著的相互作用。在OPRA队列中，LRP4多态性与总体骨折发生率显著降低（p = 0.008-0.001）和髋部骨折发生率显著降低（rs3816614, p = 0.006）相关。在OPRA队列中，观察到LRP4与BMP2和GPR177对FN骨密度以及TB和FN骨损失率的显著相互作用（p = 0.007-0.0001）。综上所述，LRP4以及LRP4与Wnt和BMP信号通路中基因的相互作用调节骨表型，包括骨量峰值和骨折，骨质疏松症的临床终点。(C) 2011爱思唯尔公司版权所有。
Osteoporosis is a common complex disorder in postmenopausal women leading to changes in the microarchitecture of bone and increased risk of fracture. Members of the low-density lipoprotein receptor-related protein (LRP) gene family regulates the development and physiology of bone through the Wnt/beta-catenin (Wnt) pathway that in turn cross-talks with the bone morphogenetic protein (BMP) pathway. In two cohorts of Swedish women: OPRA (n = 1002; age 75 years) and PEAK-25 (n = 1005; age 25 years), eleven single nucleotide polymorphisms (SNPs) from Wnt pathway genes (LRP4; LRP5; G protein-coupled receptor 177, GPR177) were analyzed for association with Bone Mineral Density (BMD), rate of bone loss, hip geometry, quantitative ultrasound and fracture. Additionally, interaction of LRP4 with LRP5, GPR177 and BMP2 were analyzed. LRP4 (rs6485702) was associated with higher total body (TB) and lumbar spine (LS) BMD in the PEAK-25 cohort (p = 0.006 and 0.005 respectively), and interaction was observed with LRP5 (p = 0.007) and BMP2 (p = 0.004) for TB BMD. LRP4 also showed significant interaction with LRP5 for femoral neck (FN) and LS BMD in this cohort. In the OPRA cohort, LRP4 polymorphisms were associated with significantly lower fracture incidence overall (p = 0.008-0.001) and fewer hip fractures (rs3816614, p = 0.006). Significant interaction in the OPRA cohort was observed for LRP4 with BMP2 and GPR177 for FN BMD as well as for rate of bone loss at TB and FN (p = 0.007-0.0001). In conclusion, LRP4 and interaction between LRP4 and genes in the Wnt and BMP signaling pathways modulate bone phenotypes including peak bone mass and fracture, the clinical endpoint of osteoporosis. (C) 2011 Elsevier Inc. All rights reserved.