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Biotin-based Pulldown Assay to Validate mRNA Targets of Cellular miRNAs
Published on: June 12, 2018
Polymorphisms in predicted miRNA binding sites and osteoporosis
Shu-Feng Lei1, Christopher J Papasian, Hong-Wen Deng
1Laboratory of Molecular and Statistical, College of Life Sciences, Hunan Normal University, Changsha, Hunan, People's Republic of China.
Summary
Genetic variations in the fibroblast growth factor 2 (FGF2) gene, specifically in microRNA binding sites, are linked to bone mineral density and osteoporosis risk. These polymorphisms may affect gene expression, influencing susceptibility to osteoporosis.
Area of Science:
- Genetics
- Molecular Biology
- Bone Biology
Background:
- MicroRNAs (miRNAs) regulate gene expression by binding to messenger RNAs (mRNAs).
- Genetic variations within miRNA binding sites on mRNAs can alter gene regulation and protein expression.
- Osteoporosis is a complex disease influenced by genetic factors affecting bone mineral density (BMD).
Purpose of the Study:
- To investigate the association between polymorphisms in miRNA target sites (poly-miRTSs) within mRNA 3'-untranslated regions (3'-UTRs) and osteoporosis.
- To identify specific genetic variations in the fibroblast growth factor 2 (FGF2) gene associated with femoral neck bone mineral density (BMD).
Main Methods:
- Utilized a database of predicted polymorphisms in miRNA target sites (poly-miRTSs).
- Conducted discovery and replication association analyses of 568 selected poly-miRTSs with osteoporosis in white subjects (total N=2725).
- Performed gene expression analyses in independent sample sets to assess FGF2 expression levels in relation to BMD.
Main Results:
- Identified three significant poly-miRTSs (rs6854081, rs1048201, rs7683093) in the FGF2 gene associated with femoral neck BMD.
- These identified FGF2 polymorphisms are potential binding sites for 9 different miRNAs, including miR-146a and miR-146b.
- FGF2 gene expression was significantly different between subjects with high and low BMD across three independent sample sets.
Conclusions:
- Three specific polymorphisms in the FGF2 gene are associated with femoral neck BMD and may contribute to osteoporosis susceptibility.
- These FGF2 gene polymorphisms likely influence osteoporosis risk by altering binding affinity for specific miRNAs, thereby affecting gene expression.
- The findings highlight the role of miRNA-mediated gene regulation in the genetic etiology of osteoporosis.
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