title: Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture.
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.
authors.affiliation: Genomics Research Center, School of Health Science, Gold Coast Campus Griffith University, Queensland, Australia.
authors.forename: Tanya
authors.initials: T
authors.lastname: Vaughan
authors.forename: Julie A
authors.initials: JA
authors.lastname: Pasco
authors.forename: Mark A
authors.initials: MA
authors.lastname: Kotowicz
authors.forename: Geoff C
authors.initials: GC
authors.lastname: Nicholson
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Morrison
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015519:Bone Density / Q000235:genetics*; D015331:Cohort Studies; D050659:Core Binding Factor Alpha 1 Subunit; D004247:DNA; D017931:DNA Primers; D005091:Exons; D005260:Female; D050723:Fractures, Bone / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D017931:DNA Primers; D009363:Neoplasm Proteins; D014157:Transcription Factors; D004247:DNA