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Association of bone morphogenetic proteins with otosclerosis

Isabelle Schrauwen, Melissa Thys, Kathleen Vanderstraeten, Erik Fransen, Nele Dieltjens, Jeroen Huyghe, Megan Ealy, Mireille Claustres, Cor Cremers, Ingeborg Dhooge UGent, et al. (2008) JOURNAL OF BONE AND MINERAL RESEARCH. 23(4). p.506-517
abstract
We studied the role of polymorphisms in 13 candidate genes on the risk of otosclerosis in two large independent case-control sets. We found significant association in both populations with BMP2 and BMP4, implicating these two genes in the pathogenesis of this disease. Introduction: Otoselerosis is a progressive disorder of the human temporal bone that leads to conductive hearing loss and in some cases sensorineural or mixed hearing loss. In a few families, it segregates as a monogenic disease with reduced penetrance, but in most patients, otosclerosis is more appropriately considered a complex disorder influenced by genetic and environmental factors. Materials and Methods: To identify major genetic factors in otosclerosis, we used a candidate gene approach to study two large independent case-control sets of Belgian-Dutch and French origin. Tag single nucleotide polymorphisms (SNPs) in 13 candidate susceptibility genes were studied in a stepwise strategy. Results: Two SNPs were identified that showed the same significant effect in both populations. The first SNP, rs3178250, is located in the 3' untranslated region of BMP2. Individuals homozygote for the C allele are protected against otosclerosis (combined populations: p = 2.2 x 10(-4); OR = 2.027; 95% CI = 1.380-2.979). The second SNP, rs17563, is an amino acid changing (p.Ala152Val) SNP located in BMP4. The G allele, coding for the amino acid alanine, confers susceptibility in both populations (combined populations: p = 0.002; OR = 1.209; 95% CI: 1.070-1.370). Conclusions: These results indicate that polymorphisms in the BMP2 and BMP4 genes, both members of the TGF-beta superfamily, contribute to the susceptibility to otosclerosis and further strengthen the results from the recently reported association of TGFBI with this disease.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
complex disease, association study, otosclerosis, bone morphogenetic proteins, otic capsule
journal title
JOURNAL OF BONE AND MINERAL RESEARCH
J. Bone Miner. Res.
volume
23
issue
4
pages
506 - 517
publisher
AMER SOC BONE & MINERAL RES, 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
Web of Science type
Article
Web of Science id
000254590000007
JCR category
ENDOCRINOLOGY & METABOLISM
JCR impact factor
6.443 (2008)
JCR rank
9/93 (2008)
JCR quartile
1 (2008)
ISSN
0884-0431
DOI
10.1359/JBMR.071112
language
English
UGent publication?
yes
classification
A1
id
688832
handle
http://hdl.handle.net/1854/LU-688832
date created
2009-06-10 15:46:56
date last changed
2016-12-19 15:46:32
@article{688832,
  abstract     = {We studied the role of polymorphisms in 13 candidate genes on the risk of otosclerosis in two large independent case-control sets. We found significant association in both populations with BMP2 and BMP4, implicating these two genes in the pathogenesis of this disease.
Introduction: Otoselerosis is a progressive disorder of the human temporal bone that leads to conductive hearing loss and in some cases sensorineural or mixed hearing loss. In a few families, it segregates as a monogenic disease with reduced penetrance, but in most patients, otosclerosis is more appropriately considered a complex disorder influenced by genetic and environmental factors.

Materials and Methods: To identify major genetic factors in otosclerosis, we used a candidate gene approach to study two large independent case-control sets of Belgian-Dutch and French origin. Tag single nucleotide polymorphisms (SNPs) in 13 candidate susceptibility genes were studied in a stepwise strategy.

Results: Two SNPs were identified that showed the same significant effect in both populations. The first SNP, rs3178250, is located in the 3' untranslated region of BMP2. Individuals homozygote for the C allele are protected against otosclerosis (combined populations: p = 2.2 x 10(-4); OR = 2.027; 95\% CI = 1.380-2.979). The second SNP, rs17563, is an amino acid changing (p.Ala152Val) SNP located in BMP4. The G allele, coding for the amino acid alanine, confers susceptibility in both populations (combined populations: p = 0.002; OR = 1.209; 95\% CI: 1.070-1.370).

Conclusions: These results indicate that polymorphisms in the BMP2 and BMP4 genes, both members of the TGF-beta superfamily, contribute to the susceptibility to otosclerosis and further strengthen the results from the recently reported association of TGFBI with this disease.},
  author       = {Schrauwen, Isabelle and Thys, Melissa and Vanderstraeten, Kathleen and Fransen, Erik and Dieltjens, Nele and Huyghe, Jeroen and Ealy, Megan and Claustres, Mireille and Cremers, Cor and Dhooge, Ingeborg and Declau, Frank and Van de Heyning, Paul and Vincent, Robert and Somers, Thomas and Offeciers, Erwin and Smith, Richard and Van Camp, Guy},
  issn         = {0884-0431},
  journal      = {JOURNAL OF BONE AND MINERAL RESEARCH},
  keyword      = {complex disease,association study,otosclerosis,bone morphogenetic proteins,otic capsule},
  language     = {eng},
  number       = {4},
  pages        = {506--517},
  publisher    = {AMER SOC BONE \& MINERAL RES, 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA},
  title        = {Association of bone morphogenetic proteins with otosclerosis},
  url          = {http://dx.doi.org/10.1359/JBMR.071112},
  volume       = {23},
  year         = {2008},
}

Chicago
Schrauwen, Isabelle, Melissa Thys, Kathleen Vanderstraeten, Erik Fransen, Nele Dieltjens, Jeroen Huyghe, Megan Ealy, et al. 2008. “Association of Bone Morphogenetic Proteins with Otosclerosis.” Journal of Bone and Mineral Research 23 (4): 506–517.
APA
Schrauwen, Isabelle, Thys, M., Vanderstraeten, K., Fransen, E., Dieltjens, N., Huyghe, J., Ealy, M., et al. (2008). Association of bone morphogenetic proteins with otosclerosis. JOURNAL OF BONE AND MINERAL RESEARCH, 23(4), 506–517.
Vancouver
1.
Schrauwen I, Thys M, Vanderstraeten K, Fransen E, Dieltjens N, Huyghe J, et al. Association of bone morphogenetic proteins with otosclerosis. JOURNAL OF BONE AND MINERAL RESEARCH. AMER SOC BONE & MINERAL RES, 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA; 2008;23(4):506–17.
MLA
Schrauwen, Isabelle, Melissa Thys, Kathleen Vanderstraeten, et al. “Association of Bone Morphogenetic Proteins with Otosclerosis.” JOURNAL OF BONE AND MINERAL RESEARCH 23.4 (2008): 506–517. Print.