Calcified Tissue International

, Volume 72, Issue 6, pp 651–658 | Cite as

Suggestive Linkage of 2p22-25 and 11q12-13 with Low Bone Mineral Density at the Lumbar Spine in the Irish Population

  • F. Wynne
  • F. J. Drummond
  • M. Daly
  • M. Brown
  • F. Shanahan
  • M. G. Molloy
  • K. A. Quane
Clinical Investigations


Osteoporosis is a disease characterized by low bone mineral density (BMD) and poor bone quality. Peak bone density is achieved by the third decade of life, after which bone is maintained by a balanced cycle of bone resorption and synthesis. Age-related bone loss occurs as the bone resorption phase outweighs the bone synthesis phase of bone metabolism. Heritability accounts for up to 90% of the variability in BMD. Chromosomal loci including 1p36, 2p22-25, 11q12-13, parathyroid hormone receptor type 1 (PTHR1), interleukin-6 (IL-6), interleukin 1 alpha (IL-1α) and type II collagen A1/vitamin D receptor (COL11A1/VDR) have been linked or shown suggestive linkage with BMD in other populations. To determine whether these loci predispose to low BMD in the Irish population, we investigated 24 microsatellite markers at 7 chromosomal loci by linkage studies in 175 Irish families of probands with primary low BMD (T-score ≤ −1.5). Nonparametric analysis was performed using the maximum likelihood variance estimation and traditional Haseman-Elston tests on the Mapmaker/Sibs program. Suggestive evidence of linkage was observed with lumbar spine BMD at 2p22-25 (maximum LOD score 2.76) and 11q12-13 (MLS 2.55). One region, 1p36, approached suggestive linkage with femoral neck BMD (MLS 2.17). In addition, seven markers achieved LOD scores >1.0, D2S149, D11S1313, D11S987, D11S1314 including those encompassing the PTHR1 (D3S3559, D3S1289) for lumbar spine BMD and D2S149 for femoral neck BMD. Our data suggest that genes within a these chromosomal regions are contributing to a predisposition to low BMD in the Irish population.


Osteoporosis Osteopenia Linkage Sib-pair Bone mineral density 



The authors are grateful to Dr. Marcella Devoto for her informative advice and discussion during this study. We would also like to thank Ms. M. Twohy, Ms. A. O’Connell and Ms. C. Tait and those general practitioners who helped in the recruitment and bleeding of individuals for the study. In addition, we would like to express our gratitude to all the patients and their families who participated in this study. Work submitted in the paper was funded by the Irish Centre for Arthritis Research and Education and an International Osteoporosis Foundation (IOF)-Servier Young Investigator Research Fellowship 2000 (FW).


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • F. Wynne
    • 1
    • 2
  • F. J. Drummond
    • 1
    • 2
  • M. Daly
    • 1
  • M. Brown
    • 3
  • F. Shanahan
    • 2
  • M. G. Molloy
    • 1
  • K. A. Quane
    • 1
    • 2
  1. 1.Department of RheumatologyNational University of Ireland, CorkIreland
  2. 2.Department of MedicineNational University of Ireland, CorkIreland
  3. 3.Spondyloarthritis and Bone Disease Research Group, OxfordEngland

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