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LRP4 association to bone properties and fracture and interaction with genes in the Wnt- and BMP signaling pathways.

Kumar, Jitender LU ; Swanberg, Maria LU ; McGuigan, Fiona LU ; Callréus, Mattias LU ; Gerdhem, Paul and Åkesson, Kristina LU (2011) In Bone 49. p.343-348
Abstract
Osteoporosis is a common complex disorder in postmenopausal women leading to changes in the micro-architecture 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/β-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 75years) and PEAK-25 (n=1005; age 25years), 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.... (More)
Osteoporosis is a common complex disorder in postmenopausal women leading to changes in the micro-architecture 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/β-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 75years) and PEAK-25 (n=1005; age 25years), 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Bone
volume
49
pages
343 - 348
publisher
Elsevier
external identifiers
  • WOS:000293805100004
  • PMID:21645651
  • Scopus:79960604475
ISSN
1873-2763
DOI
10.1016/j.bone.2011.05.018
language
English
LU publication?
yes
id
fb6266c4-560e-4f88-909b-49f5c5f0d8eb (old id 2008428)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21645651?dopt=Abstract
date added to LUP
2011-07-04 11:18:54
date last changed
2016-10-13 04:34:46
@misc{fb6266c4-560e-4f88-909b-49f5c5f0d8eb,
  abstract     = {Osteoporosis is a common complex disorder in postmenopausal women leading to changes in the micro-architecture 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/β-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 75years) and PEAK-25 (n=1005; age 25years), 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.},
  author       = {Kumar, Jitender and Swanberg, Maria and McGuigan, Fiona and Callréus, Mattias and Gerdhem, Paul and Åkesson, Kristina},
  issn         = {1873-2763},
  language     = {eng},
  pages        = {343--348},
  publisher    = {ARRAY(0xb1c20b8)},
  series       = {Bone},
  title        = {LRP4 association to bone properties and fracture and interaction with genes in the Wnt- and BMP signaling pathways.},
  url          = {http://dx.doi.org/10.1016/j.bone.2011.05.018},
  volume       = {49},
  year         = {2011},
}