Common Polymorphism in theLRP5Gene May Increase the Risk of Bone Fracture and Osteoporosis

Abstract

The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified to be linked to the variation in bone mineral density and types of bone diseases. The present study was aimed at examining the association of LRP5 rs3736228 C>T gene with bone fracture and osteoporosis by meta-analysis. A systematic electronic search of literature was conducted to identify all published studies in English or Chinese on the association of the LRP5 gene with bone fracture and osteoporosis risks. All analyses were calculated using the Version 12.0 STATA software. Odds ratios (ORs) and their corresponding 95% confidence interval (95% CI) were calculated. An updated meta-analysis was currently performed, including seven independent case-control studies. Results identified that carriers of rs3736228 C>T variant in the LRP5 gene were associated with an increased risk of developing osteoporosis and fractures under 4 genetic models but not under the dominant model (OR = 1.19, 95% CI = 0.97~1.46, and P = 0.103). Ethnicity-subgroup analysis implied that LRP5 rs3736228 C>T mutation was more likely to develop osteoporosis and fractures among Asians and Caucasians in majority of subgroups. These results suggest that there is a modest effect of the LRP5 rs3736228 C>T on the increased susceptibility of bone fracture and osteoporosis.

Dental and extra‐oral clinical features in 41 patients with WNT10A gene mutations: A multicentric genotype–phenotype study

“…Osteoblast‐specific inactivation of β‐catenin generally increases bone resorption and decreases osteoblast differentiation and bone formation . In humans, Wnt gain‐of‐function is responsible for a high bone mass phenotype whereas loss‐of‐function mutations lead to osteoporosis and an increased risk of fractures . Several types of skeletal alterations described in WNT10A heterozygous patients including severe scoliosis, asymmetrical skull geometry, maxillary brachygnathia and bilateral clinodactyly.…”

“…24 In humans, Wnt gain-of-function is responsible for a high bone mass phenotype whereas loss-of-function mutations lead to osteoporosis and an increased risk of fractures. [26][27][28] Several types of skeletal alterations described in WNT10A heterozygous patients including severe scoliosis, asymmetrical skull geometry, maxillary brachygnathia and bilateral clinodactyly. These clinical phenotypes correlate with the multiple biological functions of Wnt in bone structure regulation and homeostasis.…”

Effect of Emodin on Preventing Postoperative Intra‐Abdominal Adhesion Formation

“…Western blot was performed according to previous studies [ 24 , 32 ] to assess inflammation (COX-2) and collagen deposition ( α -SMA, MMP-9) to further delineate the mechanism of emodin (SMAD3). Mammalian protein lysis buffer (Thermo Fisher Scientific, Waltham, MA, USA) was used to extract the total tissue protein.…”

Potential damaging mutation in LRP5 from genome sequencing of the first reported chimpanzee with the Chiari malformation

“…This allows β-catenin to interact with different transcription factors that modify the expression of some important genes in osteoblasts 49 . This way, LRP5 gene plays a key role in bone homeostasis and several skeletal pathologies, such as osteoporosis, are related to mutations in its coding region 50 . Different mutations in LRP5 have been linked to reductions in bone mineral density, what could confer the individuals that present one of them susceptibility to the aforementioned osteoporosis 51 .…”