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Association of Bone Morphogenetic Proteins With Otosclerosis
Author(s) -
Schrauwen Isabelle,
Thys Melissa,
Vanderstraeten Kathleen,
Fransen Erik,
Dieltjens Nele,
Huyghe Jeroen R,
Ealy Megan,
Claustres Mireille,
Cremers Cor RWJ,
Dhooge Ingeborg,
Declau Frank,
Van de Heyning Paul,
Vincent Robert,
Somers Thomas,
Offeciers Erwin,
Smith Richard JH,
Van Camp Guy
Publication year - 2008
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.071112
Subject(s) - otosclerosis , bone morphogenetic protein , bone morphogenetic protein 5 , medicine , biology , bone morphogenetic protein 7 , genetics , audiology , gene
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 : 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. 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 × 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‐β superfamily, contribute to the susceptibility to otosclerosis and further strengthen the results from the recently reported association of TGFB1 with this disease.