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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.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|July 20, 2010
PubMed

Insights

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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