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Polymorphisms in predicted miRNA binding sites and osteoporosis
Author(s) -
Lei ShuFeng,
Papasian Christopher J,
Deng HongWen
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.186
Subject(s) - microrna , untranslated region , biology , gene , three prime untranslated region , gene expression , genetics , regulation of gene expression , gene expression profiling , messenger rna
MicroRNAs (miRNAs) regulate posttranscriptional gene expression usually by binding to 3'‐untranslated regions (3'‐UTRs) of target message RNAs (mRNAs). Hence genetic polymorphisms on 3'‐UTRs of mRNAs may alter binding affinity between miRNAs target 3'‐UTRs, thereby altering translational regulation of target mRNAs and/or degradation of mRNAs, leading to differential protein expression of target genes. Based on a database that catalogues predicted polymorphisms in miRNA target sites (poly‐miRTSs), we selected 568 polymorphisms within 3'‐UTRs of target mRNAs and performed association analyses between these selected poly‐miRTSs and osteoporosis in 997 white subjects who were genotyped by Affymetrix Human Mapping 500K arrays. Initial discovery (in the 997 subjects) and replication (in 1728 white subjects) association analyses identified three poly‐miRTSs (rs6854081, rs1048201, and rs7683093) in the fibroblast growth factor 2 ( FGF2 ) gene that were significantly associated with femoral neck bone mineral density (BMD). These three poly‐miRTSs serve as potential binding sites for 9 miRNAs (eg, miR‐146a and miR‐146b). Further gene expression analyses demonstrated that the FGF2 gene was differentially expressed between subjects with high versus low BMD in three independent sample sets. Our initial and replicate association studies and subsequent gene expression analyses support the conclusion that these three polymorphisms of the FGF2 gene may contribute to susceptibility to osteoporosis, most likely through their effects on altered binding affinity for specific miRNAs. © 2011 American Society for Bone and Mineral Research.