Calcified Tissue International

, Volume 87, Issue 1, pp 14–24 | Cite as

Analysis of Three Functional Polymorphisms in Relation to Osteoporosis Phenotypes: Replication in a Spanish Cohort

  • Lídia Agueda
  • Roser Urreizti
  • Mariona Bustamante
  • Susana Jurado
  • Natàlia Garcia-Giralt
  • Adolfo Díez-Pérez
  • Xavier Nogués
  • Leonardo Mellibovsky
  • Daniel Grinberg
  • Susana BalcellsEmail author


Osteoporosis is a complex disease involving many putative genetic factors. Association analysis of functional SNPs in candidate genes is an important tool for their identification. However, this approach is affected by limited power, population stratification, and other drawbacks that lead to discordant results. Replication in independent cohorts is essential. We performed association analyses of three functional polymorphisms previously associated with bone phenotypes—namely, Ala222Val in MTHFR, Ile1062Val in LRP6, and −13910C>T in LCT—in a cohort of 944 postmenopausal Spanish women, all of them with lumbar spine (LS) bone mineral density (BMD) data and most with femoral neck (FN) BMD and fracture data. We found significant differences between genotypes only for the MTHFR polymorphism and vertebral factures, with an OR of 2.27 (95% CI 1.17–4.38) for the TT vs. CC/CT genotypes, P = 0.018. We present genotype and allele frequency data for LCT −13910C>T for a Spanish population, where the T allele (conferring lactase persistence) has a frequency of 38.6%. Genotype frequencies were consistent with observed clines in Europe and with the prevalence of lactase nonpersistence. The LCT −13910C>T polymorphism was significantly associated with height and weight, such that T allele carriers were 0.88 cm taller (95% CI 0.08–1.59 cm, P = 0.032, adjusted by age) than CC individuals and TT homozygotes were 1.91 kg heavier than CC/CT individuals (95% CI 0.11–3.71 kg, P = 0.038, adjusted by age). In conclusion, no significant association was observed between the studied polymorphisms and LS BMD or FN BMD in postmenopausal Spanish women, and only MTHFR Ala222Val was associated with vertebral fractures.


MTHFR LCT LRP6 Association study BMD Fracture 



The authors are grateful to M. Cozar for technical help and R. Rycroft for revising the English. They also thank B. Obermayer for sharing the LCT genotyping assay information. L. A. is the recipient of a fellowship from the Catalan government. This study was supported by grants from the Carlos III Health Institute (ISCIII), Spanish Ministry of Science and Innovation (PI030708), Spanish Ministry of Education and Science (SAF2007-64654), and Catalan government (2005SGR 00848 and 2009SGR971). The authors are also grateful for the support from the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) and the Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF), which are initiatives of the ISCIII.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Lídia Agueda
    • 1
    • 2
    • 3
  • Roser Urreizti
    • 1
    • 2
    • 3
  • Mariona Bustamante
    • 1
    • 2
    • 3
  • Susana Jurado
    • 4
    • 5
  • Natàlia Garcia-Giralt
    • 4
    • 5
  • Adolfo Díez-Pérez
    • 4
    • 5
  • Xavier Nogués
    • 4
    • 5
  • Leonardo Mellibovsky
    • 4
    • 5
  • Daniel Grinberg
    • 1
    • 2
    • 3
  • Susana Balcells
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Genetics, Faculty of BiologyUniversity of BarcelonaBarcelonaSpain
  2. 2.Institut de Biomedicina de la Universitat de Barcelona (IBUB)BarcelonaSpain
  3. 3.CIBER de Enfermedades Raras (CIBERER)BarcelonaSpain
  4. 4.Internal Medicine, URFOA, IMIM, Hospital del MarAutonomous University of BarcelonaBarcelonaSpain
  5. 5.Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF)BarcelonaSpain

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