Alleles of RUNX2/CBFA1 Gene Are Associated With Differences in Bone Mineral Density and Risk of Fracture

Authors

  • Tanya Vaughan,

    1. Genomics Research Center, School of Health Science, Gold Coast Campus Griffith University, Queensland, Australia
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  • Julie A. Pasco,

    1. Clinical and Biomedical Health Sciences-Barwon Health, The University of Melbourne, The Geelong Hospital, Geelong, Australia
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  • Mark A. Kotowicz,

    1. Clinical and Biomedical Health Sciences-Barwon Health, The University of Melbourne, The Geelong Hospital, Geelong, Australia
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  • Geoff C. Nicholson,

    1. Clinical and Biomedical Health Sciences-Barwon Health, The University of Melbourne, The Geelong Hospital, Geelong, Australia
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  • Nigel A. Morrison Ph.D.

    Corresponding author
    1. Genomics Research Center, School of Health Science, Gold Coast Campus Griffith University, Queensland, Australia
    • Genomics Research Centre, School of Health Science, Gold Coast Campus Griffith University, Queensland 9726, Australia
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  • The authors have no conflict of interest.

Abstract

The aim of this study was to determine if DNA polymorphism within runt-related gene 2 (RUNX2)/core binding factor A1 (CBFA1) is related to bone mineral density (BMD). RUNX2 contains a glutamine-alanine repeat where mutations causing cleidocranial dysplasia (CCD) have been observed. Two common variants were detected within the alanine repeat: an 18-bp deletion and a synonymous alanine codon polymorphism with alleles GCA and GCG (noted as A and G alleles, respectively). In addition, rare mutations that may be related to low BMD were observed within the glutamine repeat. In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The effect was maximal at the ultradistal (UD) radius (p = 0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture, suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis.

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