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Calcified Tissue International
Published in: Calcified Tissue International 2/2003

01-08-2003 | Clinical Investigations

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

Authors: L. D. Spotila, H. Rodriguez, M. Koch, H. S. Tenenhouse, A. Tenenhouse, H. Li, M. Devoto

Published in: Calcified Tissue International | Issue 2/2003

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Abstract

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.
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Metadata
Title
Association Analysis of Bone Mineral Density and Single Nucleotide Polymorphisms in Two Candidate Genes on Chromosome 1p36
Authors
L. D. Spotila
H. Rodriguez
M. Koch
H. S. Tenenhouse
A. Tenenhouse
H. Li
M. Devoto
Publication date
01-08-2003
Publisher
Springer-Verlag
Published in
Calcified Tissue International / Issue 2/2003
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-002-2079-1

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