Osteoporosis International

, Volume 19, Issue 12, pp 1769–1775

Replication of associations between LRP5 and ESRRA variants and bone density in premenopausal women

  • S. Giroux
  • L. Elfassihi
  • D. E. C. Cole
  • F. Rousseau
Original Article

Abstract

Summary

Replication is a critical step to validate positive genetic associations. In this study, we tested two previously reported positive associations. The low density lipoprotein receptor-related protein 5 (LRP5) Val667Met and lumbar spine bone density are replicated. This result is in line with results from large consortiums such as Genomos. However, the estrogen-related receptor alpha (ESRRA) repeat in the promoter is not replicated although the polymorphism studied was functional and could have been a causative variant.

Introduction

We sought to validate associations previously reported between LRP5 V667M polymorphism and lumbar spine (LS, p = 0.013) and femoral neck (FN, p = 0.0002) bone mineral density (BMD), and between ESRRA 23 base pair repeat polymorphism and LS BMD (p = 0.0036) in a sample of premenopausal Caucasian women using an independent sample.

Methods

For the replication sample, we recruited 673 premenopausal women from the Toronto metropolitan area. All women were Caucasian and had BMD measured. LRP5 V667M was genotyped by allele-specific PCR and ESRRA repeats by sizing of PCR products on agarose gels.

Results

We reproduced the same association as we reported previously between LRP5 V667M and LS BMD (p = 0.015) but not with FN BMD (p = 0.254). The combined data from the two populations indicate an effect size of 0.28SD for LS BMD (p = 0.00048) and an effect size of 0.26 SD for FN BMD (p = 0.00037). In contrast, the association we reported earlier between ESRRA repeats and LS BMD was not replicated in the sample from Toronto (p = 0.645).

Conclusions

The association between LRP5 V667M and LS BMD is confirmed but not that between ESRRA repeats and LS BMD. This result indicates that it is imperative to validate any positive association in an independent sample.

Keywords

Bone density Complex trait Genetic association Polymorphism Replication 

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Authors and Affiliations

  • S. Giroux
    • 1
  • L. Elfassihi
    • 1
    • 2
  • D. E. C. Cole
    • 3
    • 4
  • F. Rousseau
    • 1
    • 2
    • 5
  1. 1.Centre de Recherche de l’Hôpital, St-François d’AssiseCentre Hospitalier Universitaire de QuébecQuebecCanada
  2. 2.Faculty of MedicineLaval UniversityQuebecCanada
  3. 3.Department of Clinical Pathology, Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada
  4. 4.Department of Laboratory Medicine & PathobiologyUniversity of TorontoTorontoCanada
  5. 5.Centre for the Development, Evaluation and Rational Implementation of New Diagnostic Tools in Medicine (CEDERINDT)/The CanGèneTest research consortium on genetic laboratory servicesQuebecCanada

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