Journal
BONE
Volume 49, Issue 3, Pages 343-348Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2011.05.018
Keywords
Association study; Bone Mineral Density; Fracture; Osteoporosis; Polymorphism
Categories
Funding
- Swedish Research Council [K2009-53X-14691-07-3]
- FAS [2007-2125]
- Greta and Johan Kock Foundation
- A. Pahlsson Foundation
- A. Osterlund Foundation
- H. Jarnhardt Foundation
- King Gustav V and Queen Victoria Foundation
- Malmo University Hospital Research Foundation
- Research and Development Council of Region Skane, Sweden
- Swedish Medical Society
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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.
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