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

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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, r 2 = 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.

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Acknowledgments

Robin Rycroft provided editorial assistance. MB and LA were recipients of fellowships from the Spanish Ministerio de Ciencia y Tecnología and Generalitat de Catalunya, respectively. This study was supported by grants from the Spanish Ministerio de Ciencia y Tecnología (PM1999-0131-C02-01), the Spanish Ministerio de Educación y Ciencia (SAF2004-06085), the European Commission (GENOMOS Project grant QLRT-2001-02629), the Spanish Ministerio de Sanidad (FIS 98/1952), and the Catalan Departament de Universitats, Recerca i Societat de la Informació (2005SGR 00762 and 2005SGR 00848).

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Authors and Affiliations

  1. Department of Genetics, University of Barcelona, Av. Diagonal, 645, E-08028, Barcelona, Spain

    Mariona Bustamante, Lídia Águeda, Anke Wesselius, Susana Balcells & Daniel Grinberg

  2. Institut de Biomedicina UB (IBUB), Diagonal 645, 08028, Barcelona, Spain

    Mariona Bustamante, Lídia Águeda, Susana Balcells & Daniel Grinberg

  3. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), Av. Diagonal 645, 08028, Barcelona, Spain

    Mariona Bustamante, Lídia Águeda, Susana Balcells & Daniel Grinberg

  4. Department of Internal Medicine, Unitat de Recerca en Fisipatologia Òssia i Articular (URFOA), Institut Municipal d’Investigació Mèdica (IMIM), Hospital del Mar, Autonomous University of Barcelona, Dr. Aiguader 88, 08003, Barcelona, Spain

    Xavier Nogués, Susana Jurado, Leonardo Mellibovsky & Adolfo Díez-Pérez

  5. Department of Traumathology and Orthopaedics Surgery, URFOA, IMIM, Hospital del Mar, Autonomous University of Barcelona, Dr. Aiguader 88, 08003, Barcelona, Spain

    Enrique Cáceres

  6. Department of Gynecology and Obstetrics, URFOA, IMIM, Hospital del Mar, Autonomous University of Barcelona, Dr. Aiguader 88, 08003, Barcelona, Spain

    Ramon Carreras

  7. Department of Rheumathology, URFOA, IMIM, Hospital del Mar, Autonomous University of Barcelona, Dr. Aiguader 88, 08003, Barcelona, Spain

    Manel Ciria

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  1. Mariona Bustamante
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  2. Xavier Nogués
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  3. Lídia Águeda
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  4. Susana Jurado
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  5. Anke Wesselius
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  6. Enrique Cáceres
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  7. Ramon Carreras
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  8. Manel Ciria
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  9. Leonardo Mellibovsky
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  11. Adolfo Díez-Pérez
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  12. Daniel Grinberg
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Corresponding author

Correspondence to Daniel Grinberg.

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Bustamante, M., Nogués, X., Águeda, L. et al. Promoter 2 -1025 T/C Polymorphism in the RUNX2 Gene Is Associated with Femoral Neck BMD in Spanish Postmenopausal Women. Calcif Tissue Int 81, 327–332 (2007). https://doi.org/10.1007/s00223-007-9069-2

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  • DOI: https://doi.org/10.1007/s00223-007-9069-2

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