The Polymorphism at PLCB4 Promoter (rs6086746) Changes the Binding Affinity of RUNX2 and Affects Osteoporosis Susceptibility: An Analysis of Bioinformatics-Based Case-Control Study and Functional Validation
Abstract
Purpose Genome-wide association studies have identified numerous genetic variants that are associated with osteoporosis risk; however, most of them are present in the non-coding regions of the genome and the functional mechanisms are unknown. In this study, we aimed to investigate the potential variation in runt domain transcription factor 2 (RUNX2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding variants within RUNX2 binding sites and risk of osteoporosis in postmenopausal osteoporosis (PMOP). Methods We performed bioinformatics-based prediction by combining whole genome sequencing and chromatin immunoprecipitation sequencing to screen functional SNPs in the RUNX2 binding site using data from the database of Taiwan Biobank; Case-control studies with 651 postmenopausal women comprising 107 osteoporosis patients, 290 osteopenia patients, and 254 controls at Tri-Service General Hospital between 2015 and 2019 were included. The subjects were examined for bone mass density and classified into normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Furthermore, mRNA expression and luciferase reporter assay were used to provide additional evidence regarding the associations identified in the association analyses. Chi-square tests and logistic regression were mainly used for statistical assessment. Results Through candidate gene approaches, 3 SNPs in…
How strong is the evidence?
Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 651 participants or records.
Read the paper
Related studies
- Irisin Enhances Osteoblast DifferentiationIn Vitro
- Glucocorticoids suppress Wnt16 expression in osteoblasts in vitro and in vivo
- Interaction between Schwann Cells and Osteoblasts In Vitro
- Administration of cinnamaldehyde promotes osteogenesis in ovariectomized rats and differentiation of osteoblast in vitro
- The Effect of the Major Components of Fructus Cnidii on Osteoblasts In Vitro
- Estrogen depletion alters osteogenic differentiation and matrix production by osteoblasts in vitro
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.