PMID- 20641033 OWN - NLM STAT- MEDLINE DCOM- 20110330 LR - 20211020 IS - 1523-4681 (Electronic) IS - 0884-0431 (Print) IS - 0884-0431 (Linking) VI - 26 IP - 1 DP - 2011 Jan TI - Polymorphisms in predicted miRNA binding sites and osteoporosis. PG - 72-8 LID - 10.1002/jbmr.186 [doi] AB - 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. CI - (c) 2011 American Society for Bone and Mineral Research. FAU - Lei, Shu-Feng AU - Lei SF AD - Laboratory of Molecular and Statistical, College of Life Sciences, Hunan Normal University, Changsha, Hunan, People's Republic of China. FAU - Papasian, Christopher J AU - Papasian CJ FAU - Deng, Hong-Wen AU - Deng HW LA - eng GR - R01AR050496/AR/NIAMS NIH HHS/United States GR - RC2 DE020756/DE/NIDCR NIH HHS/United States GR - R01 AG026564/AG/NIA NIH HHS/United States GR - P50AR055081/AR/NIAMS NIH HHS/United States GR - RC2DE020756/DE/NIDCR NIH HHS/United States GR - R01 AR057049/AR/NIAMS NIH HHS/United States GR - P50 AR055081/AR/NIAMS NIH HHS/United States GR - R03 TW008221/TW/FIC NIH HHS/United States GR - R01 AR050496/AR/NIAMS NIH HHS/United States GR - R01AG026564/AG/NIA NIH HHS/United States GR - R03TW008221/TW/FIC NIH HHS/United States GR - R01AR057049/AR/NIAMS NIH HHS/United States GR - CAPMC/CIHR/Canada PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - J Bone Miner Res JT - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JID - 8610640 RN - 0 (MicroRNAs) RN - 103107-01-3 (Fibroblast Growth Factor 2) SB - IM MH - Binding Sites MH - Bone Density/genetics MH - Female MH - Femur Neck/physiopathology MH - Fibroblast Growth Factor 2/genetics/metabolism MH - Gene Expression Regulation MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Humans MH - Male MH - MicroRNAs/*genetics/metabolism MH - Middle Aged MH - Osteoporosis/*genetics/physiopathology MH - Polymorphism, Single Nucleotide/*genetics MH - Reproducibility of Results PMC - PMC3179316 EDAT- 2010/07/20 06:00 MHDA- 2011/03/31 06:00 PMCR- 2012/01/01 CRDT- 2010/07/20 06:00 PHST- 2010/07/20 06:00 [entrez] PHST- 2010/07/20 06:00 [pubmed] PHST- 2011/03/31 06:00 [medline] PHST- 2012/01/01 00:00 [pmc-release] AID - 10.1002/jbmr.186 [doi] PST - ppublish SO - J Bone Miner Res. 2011 Jan;26(1):72-8. doi: 10.1002/jbmr.186.