Polyalanine repeat polymorphism in RUNX2 is associated with site-specific fracture in post-menopausal females

Morrison, Nigel A., Stephens, Alexandre S., Osato, Motomi, Pasco, Julie A., Fozzard, Nicolette, Stein, Gary S., Polly, Patsie, Griffiths, Lyn R. and Nicholson, Geoff C. (2013) Polyalanine repeat polymorphism in RUNX2 is associated with site-specific fracture in post-menopausal females. PLoS ONE, 8 9: e72740.1-e72740.8. doi:10.1371/journal.pone.0072740


Author Morrison, Nigel A.
Stephens, Alexandre S.
Osato, Motomi
Pasco, Julie A.
Fozzard, Nicolette
Stein, Gary S.
Polly, Patsie
Griffiths, Lyn R.
Nicholson, Geoff C.
Title Polyalanine repeat polymorphism in RUNX2 is associated with site-specific fracture in post-menopausal females
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-09-23
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0072740
Open Access Status DOI
Volume 8
Issue 9
Start page e72740.1
End page e72740.8
Total pages 9
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2014
Language eng
Subject 1100 Agricultural and Biological Sciences
1300 Biochemistry, Genetics and Molecular Biology
2700 Medicine
Abstract 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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