Calcified Tissue International

, Volume 81, Issue 4, pp 327–332

Promoter 2 -1025 T/C Polymorphism in the RUNX2 Gene Is Associated with Femoral Neck BMD in Spanish Postmenopausal Women

  • Mariona Bustamante
  • Xavier Nogués
  • Lídia Águeda
  • Susana Jurado
  • Anke Wesselius
  • Enrique Cáceres
  • Ramon Carreras
  • Manel Ciria
  • Leonardo Mellibovsky
  • Susana Balcells
  • Adolfo Díez-Pérez
  • Daniel Grinberg
Article

DOI: 10.1007/s00223-007-9069-2

Cite this article as:
Bustamante, M., Nogués, X., Águeda, L. et al. Calcif Tissue Int (2007) 81: 327. doi:10.1007/s00223-007-9069-2

Abstract

Stimulation of bone formation is a key therapeutic target in osteoporosis. Runx2 is a runt domain transcription factor essential to osteoblast differentiation, bone remodeling, and fracture healing. Runx2 knockout mice exhibit a complete lack of ossification, while overexpression of this gene in transgenic mice results in an osteoporotic phenotype. Thus, RUNX2 is a good candidate for the genetic determination of osteoporosis. In this association study, the effects of the -330 G/T polymorphism in promoter 1 and the -1025 T/C polymorphism (rs7771980) in promoter 2 of RUNX2 were tested in relation to lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) in a cohort of 821 Spanish postmenopausal women. The minor allele frequencies for the two polymorphisms were 0.15 and 0.07, respectively. The two polymorphisms, located more than 90 kb apart, were not in linkage disequilibrium (D′ = 0.27, r2 = 0.028). In an ANCOVA test adjusting by weight, height, age, and years since menopause, the -330 G/T polymorphism was not associated with any of the phenotypes analyzed, while we found the -1025 T/C polymorphism to be associated with FN BMD (p = 0.001). In particular, individuals carrying the TC genotype had higher mean adjusted FN BMD values than those bearing the TT genotype. Our results highlight the importance of this RUNX2 promoter 2 polymorphism in FN BMD determination.

Keywords

Osteoporosis BMD Association RUNX2 CBFA1 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Mariona Bustamante
    • 1
    • 2
    • 3
  • Xavier Nogués
    • 4
  • Lídia Águeda
    • 1
    • 2
    • 3
  • Susana Jurado
    • 4
  • Anke Wesselius
    • 1
  • Enrique Cáceres
    • 5
  • Ramon Carreras
    • 6
  • Manel Ciria
    • 7
  • Leonardo Mellibovsky
    • 4
  • Susana Balcells
    • 1
    • 2
    • 3
  • Adolfo Díez-Pérez
    • 4
  • Daniel Grinberg
    • 1
    • 2
    • 3
  1. 1.Department of GeneticsUniversity of BarcelonaBarcelonaSpain
  2. 2.Institut de Biomedicina UB (IBUB)BarcelonaSpain
  3. 3.Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII)BarcelonaSpain
  4. 4.Department of Internal MedicineUnitat de Recerca en Fisipatologia Òssia i Articular (URFOA), Institut Municipal d’Investigació Mèdica (IMIM), Hospital del Mar, Autonomous University of BarcelonaBarcelonaSpain
  5. 5.Department of Traumathology and Orthopaedics SurgeryURFOA, IMIM, Hospital del Mar, Autonomous University of BarcelonaBarcelonaSpain
  6. 6.Department of Gynecology and ObstetricsURFOA, IMIM, Hospital del Mar, Autonomous University of BarcelonaBarcelonaSpain
  7. 7.Department of RheumathologyURFOA, IMIM, Hospital del Mar, Autonomous University of BarcelonaBarcelonaSpain