Association of bone morphogenetic proteins with otosclerosis

Isabelle Schrauwen; Melissa Thys; Kathleen Vanderstraeten; Erik Fransen; Nele Dieltjens; Jeroen R Huyghe; Megan Ealy; Mireille Claustres; Cor R W J Cremers; Ingeborg Dhooge; Frank Declau; Paul Van de Heyning; Robert Vincent; Thomas Somers; Erwin Offeciers; Richard J H Smith; Guy Van Camp

doi:10.1359/jbmr.071112

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Association of bone morphogenetic proteins with otosclerosis

Journal article

Open access

Peer reviewed

Association of bone morphogenetic proteins with otosclerosis

Isabelle Schrauwen, Melissa Thys, Kathleen Vanderstraeten, Erik Fransen, Nele Dieltjens, Jeroen R Huyghe, Megan Ealy, Mireille Claustres, Cor R W J Cremers, Ingeborg Dhooge, …

Journal of bone and mineral research, Vol.23(4), pp.507-516

04/2008

DOI: 10.1359/jbmr.071112

PMCID: PMC2669162

PMID: 18021008

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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. Otosclerosis 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. 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. 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). 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 TGFB1 with this disease.

Bone Morphogenetic Protein 4

Bone Morphogenetic Proteins - physiology

Bone Morphogenetic Protein 2

Humans

Transforming Growth Factor beta - physiology

Male

Case-Control Studies

Otosclerosis - physiopathology

Hearing Loss - genetics

Transforming Growth Factor beta - genetics

Female

Otosclerosis - genetics

Polymorphism, Single Nucleotide

Bone Morphogenetic Proteins - genetics

Details

Title: Subtitle: Association of bone morphogenetic proteins with otosclerosis
Creators: Isabelle Schrauwen - Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
Melissa Thys
Kathleen Vanderstraeten
Erik Fransen
Nele Dieltjens
Jeroen R Huyghe
Megan Ealy
Mireille Claustres
Cor R W J Cremers
Ingeborg Dhooge
Frank Declau
Paul Van de Heyning
Robert Vincent
Thomas Somers
Erwin Offeciers
Richard J H Smith
Guy Van Camp
Resource Type: Journal article
Publication Details: Journal of bone and mineral research, Vol.23(4), pp.507-516
DOI: 10.1359/jbmr.071112
PMID: 18021008
PMCID: PMC2669162
NLM abbreviation: J Bone Miner Res
ISSN: 0884-0431
eISSN: 1523-4681
Publisher: United States
Grant note: T32 GM008629 / NIGMS NIH HHS R01DC05218 / NIDCD NIH HHS R01 DC005218 / NIDCD NIH HHS
Language: English
Date published: 04/2008
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006404602771

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