FGF2 gene polymorphisms linked to increased risk for osteoporosis
MedWire News: Three polymorphisms in the fibroblast growth factor (FGF)2 gene may increase the risk for developing osteoporosis, suggest findings showing significant associations of the variants with femoral neck bone mineral density (BMD) in White individuals.
"Polymorphisms in 3'-untranslated regions (3'-UTRs) of messenger RNAs (mRNAs) potentially could alter the affinity of microRNAs (miRNAs) for their target mRNAs. This altered affinity could affect the efficiency with which microRNAs (miRNAs) regulate protein expression," comment Hong-Wen Deng (Hunan Normal University, China) and co-authors.
The findings may have therapeutic implications as higher levels of FGF proteins would stimulate osteoclastogenesis, which would enhance bone resorption and consequently lower BMD in affected individuals.
For the study, Deng and team selected 568 polymorphisms within 3'-UTRs of target mRNAs from a database cataloguing predicted polymorphisms in miRNAs target sites (poly-miRTSs).
Association analyses were performed between the selected 568 poly-miRTSs and osteoporosis in 997 genotyped White individuals. Replication association analyses were performed in an additional 1728 women. All individuals were aged 50.3-51.6 years.
The researchers identified three poly-miRTSs (rs6854081, rs1048201, and rs7683093) in the FGF2 gene that were significantly associated with femoral neck BMD, which function as potential binding sites for nine miRNAs.
Indeed, three separate sample sets showed that individuals with high hip BMD had significantly lower expression of the FGF2 gene compared with those showing low hip BMD values.
"The data from association analyses at the DNA level and gene expression analyses at the RNA level are consistent in supporting the concept that polymorphisms detected in the FGF2 gene regulate BMD variation, possible by altering the affinity of mRNA products for specific miRNAs," say Deng et al.
"Extensive functional studies will be required to confirm this proposed hypothetical mechanism by which poly-miRTSs regulate BMD," conclude the authors in the Journal of Bone Mineral Research.
By Ingrid Grasmo