| Title: |
Polyalanine Repeat Polymorphism in RUNX2 Is Associated with Site-Specific Fracture in Post-Menopausal Females |
| Authors: |
Morrison, NA; Stephens, AS; Osato, M; Pasco, JA; Fozzard, N; Stein, GS; Polly, P; Griffiths, LR; Nicholson, GC |
| Contributors: |
Grant, SFA |
| Publisher Information: |
PUBLIC LIBRARY SCIENCE |
| Publication Year: |
2013 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
Runt related transcription factor 2 (RUNX2) is a key regulator of osteoblast differentiation. Several variations within the RUNX2 gene have been found to be associated with significant changes in BMD, which is a major risk factor for fracture. In this study we report that an 18 bp deletion within the polyalanine tract (17A>11A) of RUNX2 is significantly associated with fracture. Carriers of the 11A allele were found to be nearly twice as likely to have sustained fracture. Within the fracture category, there was a significant tendency of 11A carriers to present with fractures of distal radius and bones of intramembranous origin compared to bones of endochondral origin (p = 0.0001). In a population of random subjects, the 11A allele was associated with decreased levels of serum collagen cross links (CTx, p = 0.01), suggesting decreased bone turnover. The transactivation function of the 11A allele showed a minor quantitative decrease. Interestingly, we found no effect of the 11A allele on BMD at multiple skeletal sites. These findings suggest that the 11A allele is a biologically relevant polymorphism that influences serum CTx and confers enhanced fracture risk in a site-selective manner related to intramembranous bone ossification. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1932-6203 |
| Relation: |
https://hdl.handle.net/11343/263289 |
| Availability: |
https://hdl.handle.net/11343/263289 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.4114BBC5 |
| Database: |
BASE |