Calcified Tissue International

, Volume 73, Issue 2, pp 140–146

Association Analysis of Bone Mineral Density and Single Nucleotide Polymorphisms in Two Candidate Genes on Chromosome 1p36

  • L. D. Spotila
  • H. Rodriguez
  • M. Koch
  • H. S. Tenenhouse
  • A. Tenenhouse
  • H. Li
  • M. Devoto
Clinical Investigations


Two candidate genes for bone mineral density (BMD), tumor necrosis factor alpha receptor 2 (TNFRSF1B) and lysyl hydroxylase (PLOD1), have been scanned for single nucleotide polymorphisms (SNPs) within their coding and promoter regions. These two genes, separated by about 200 kb, are located within the chromosomal interval 1p36.2–1p36.3 that has been linked to femoral neck BMD. In a patient population (n = 104) of European descent, there were four SNPs within TNFRSF1B and six SNPs within PLOD1 that occurred with greater than 5% frequency. There was significant linkage disequilibrium within both genes. Single marker analysis revealed significant association for one SNP located in intron 6 of PLOD1 and lumbar spine BMD (P = 0.01). Allelic haplotypes that encompassed the four SNPs in TNFRSF1B or the six SNPs in PLOD1 were assigned using a Bayesian algorithm as implemented in the program Haplotyper. Association of TNFRSF1B haplotypes with femoral neck BMD was statistically significant (P = 0.01). Similarly, PLOD1 haplotypes demonstrated a statistically significant association with spinal BMD (P = 0.04). These findings strengthen the potential importance of chromosome 1p36.2–1p36.3 in contributing to BMD variation, and are consistent with genetic variation in either PLOD1, TNFRSF1B or nearby genes playing a role in the phenotype.


TNFRSF1B PLOD1 Osteoporosis Association study Haplotype analysis 


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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • L. D. Spotila
    • 1
  • H. Rodriguez
    • 1
  • M. Koch
    • 1
  • H. S. Tenenhouse
    • 3
  • A. Tenenhouse
    • 4
  • H. Li
    • 2
  • M. Devoto
    • 2
    • 5
  1. 1.Department of Bioscience and BiotechnologyDrexel University, Philadelphia, PA 19104USA
  2. 2.Department of ResearchNemours Children’s Clinic-Wilmington, Wilmington, DE 19899USA
  3. 3.Department of Pediatrics and Human GeneticsMcGill University, Children’s Hospital Research Institute, Montreal, Quebec H3Z 2Z3Canada
  4. 4.Metabolic Bone CentreMontreal General Hospital, Montreal, Quebec H3G 1A4Canada
  5. 5.Department of Oncology, Biology, and GeneticsUniversity of Genoa, GenoaItaly

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