Journal of Bone and Mineral Metabolism

, Volume 24, Issue 3, pp 226–234 | Cite as

Assessment of linkage and association of 13 genetic loci with bone mineral density

  • Helen H.L. Lau
  • Mandy Y.M. Ng
  • William M.W. Cheung
  • Andrew D. Paterson
  • Pak C. Sham
  • Keith D.K. Luk
  • Vivian Chan
  • Annie W.C. Kung


Bone mineral density (BMD), an important risk factor for osteoporosis, is a complex trait likely affected by multiple genes. The linkage and/or association of 13 polymorphic loci of seven candidate genes (estrogen receptor alpha [ERα] and beta [ERβ], calcium-sensing receptor, vitamin D receptor, collagen type 1α1, low-density lipoprotein [LDL] receptor-related protein 5 [LRPS], and transforming growth factor β1) were evaluated in 177 southern Chinese pedigrees of 674 subjects, with each pedigree identified through a proband having a BMD Z score of −1.28 or less at the hip or spine. A suggestive linkage was detected between the IVS1-351A/G polymorphism of ERα and spine BMD, and between the 1082G/A, 1730G/A, and D14S1026 polymorphisms of ERβ and BMD at both spine and hip. The quantitative transmission disequilibrium test (QTDT) detected total family association between 1730G/A of ERβ and BMD at spine and hip; between D14S1026 of ERβ and hip BMD; and between the 266A/G and 2220C/T polymorphisms of LRP5 and hip BMD. Similar total family associations were detected when only the females were analyzed. In addition, the IVS1-397T/C polymorphism of ERα was associated with spine BMD, and the 266A/G and 2220C/T polymorphisms of LRP5 were associated with femoral neck BMD in the females. A within-family association was detected with the IVS1-397T/C polymorphism of ERα, and the 266A/G and 2220C/T polymorphisms of LRP5 in the females. The effect of each polymorphism on BMD variance ranged from 1% to 4%. In conclusion, ERα, ERβ and LRP5 are important candidate genes determining BMD variation, especially in females.

Key words

BMD candidate genes association linkage 


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Copyright information

© Springer-Verlag Tokyo 2006

Authors and Affiliations

  • Helen H.L. Lau
    • 1
  • Mandy Y.M. Ng
    • 1
    • 2
  • William M.W. Cheung
    • 1
  • Andrew D. Paterson
    • 3
  • Pak C. Sham
    • 2
    • 4
    • 5
  • Keith D.K. Luk
    • 6
  • Vivian Chan
    • 1
  • Annie W.C. Kung
    • 1
  1. 1.Department of MedicineThe University of Hong Kong, Queen Mary Hospital, PokfulamHong KongChina
  2. 2.Genome Research CentreThe University of Hong Kong, PokfulamHong KongChina
  3. 3.Program in Genetics and Genomic Biology, Hospital for Sick Children, and Department of Public Health SciencesUniversity of TorontoTorontoCanada
  4. 4.Department of PsychiatryThe University of Hong Kong, PokfulamHong KongChina
  5. 5.Institute of PsychiatryKing's College of MedicineLondonUnited Kingdom
  6. 6.Department of Orthopaedic Surgery and TraumatologyThe University of Hong Kong, PokfulamHong KongChina

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