Relation Between Renin-Angiotensin-Aldosterone System and Otosclerosis

Imauchi, Yutaka; Jeunemaı̂tre, Xavier; Boussion, Magali; Ferrary, Évelyne; Sterkers, Olivier; Grayeli, Alexis Bozorg

doi:10.1097/mao.0b013e318164d12c

Cited by 39 publications

(1 citation statement)

References 25 publications

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“…Specific causative genes within these loci, which contain many genes, remain to be identified. Genetic association studies, however, have implicated specific genes in pathogenesis of otosclerosis: COL1A1 (McKenna et al, 1998), TGFB1 (Thys et al, 2009), BMP2 (Schrauwen et al, 2008), BMP4 (Schrauwen et al, 2008) angiotensin I AGT (Imauchi et al, 2008), angiotensin I converting enzyme (ACE, Imauchi et al, 2008), and reelin (RELN, Schrauwen et al, 2009; Schrauwen et al, 2009b). Only COL1A1 was known at the time we began the current st udy.…”

Section: Discussionmentioning

confidence: 99%

Differences in gene expression between the otic capsule and other bones

et al. 2010

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Our long term goal is to understand the molecular pathology of otosclerosis and to develop better forms of therapy. Toward this goal, the current study focused on characterizing the molecular factors responsible for the unique biological features of the otic capsule: its minimal rate of remodeling, and lack of healing capacity when fractured. We compared expression levels of 62 genes involved in bone metabolism between the adult murine otic capsule and the tibia and parietal bones; the latter exemplify bones formed by endochondral and intramembranous ossification, respectively. Gene expression levels were measured using real-time quantitative RT-PCR and analyzed using tools of bioinformatics. Expression patterns of key genes were verified with in situ hybridization. The molecular profile of the otic capsule was distinctly different from that of the tibia and parietal bone. Genes found to be most characteristic of the otic capsule were: osteoprotegerin (opg), bone morphogenetic protein receptor 1b (bmpr1b) and bone morphogenetic protein 3 (bmp3). Expression levels were high for opg and bmpr1b, and minimal for bmp3 within the otic capsule. We concluded that opg and bmpr1b likely play important roles in inhibition of remodeling within the otic capsule.

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Section: Discussionmentioning

confidence: 99%

Differences in gene expression between the otic capsule and other bones

et al. 2010

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COL1A1 association and otosclerosis: A meta‐analysis

Schrauwen

Khalfallah

Ealy

et al. 2012

American J of Med Genetics Pt A

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Otosclerosis is a disease of abnormal bone remodeling in the human otic capsule that can lead to progressive hearing loss. Little of the underlying disease etiology has been elucidated thus far, although several studies have suggested that COL1A1 may play a role based on its importance in bone metabolism and other diseases like osteoporosis and osteogenesis imperfecta. Genetic association studies between COL1A1 and otosclerosis, however, have been contradictory. To resolve this issue, we studied a large Belgian-Dutch and a Swiss population for a genetic association between COL1A1 and otosclerosis and additionally performed a meta-analysis to investigate the overall genetic effect of COL1A1 on all otosclerosis populations studied to date. We found a significant association both in the Belgian-Dutch population and in the meta-analysis. In aggregate, our analysis supports evidence for an association between COL1A1 and otosclerosis although effect sizes of the variants reported in the initial studies are likely to be an overestimate of true effect sizes.

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The etiology of otosclerosis: A combination of genes and environment

Schrauwen

Camp

2010

The Laryngoscope

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Otosclerosis is a common form of hearing loss characterized by abnormal bone remodeling in the otic capsule. It is a complex genetic disease, caused by a combination of genetic and environmental factors. During the past decade, several attempts have been made to identify factors for otosclerosis. This review provides an overview of the current understanding of the etiology of otosclerosis and describes the genetic and environmental factors that have been implicated in the disease. Environmental factors include fluoride and viral factors, particularly measles. Genetic association studies for otosclerosis have reported several associations of genetic variants that influence the risk of disease, mainly involving bone remodeling pathways, although their individual risk contributions are small. Rare monogenic forms of otosclerosis also exist, which are caused by a mutation in a single gene leading to a clear familial segregation of the disease. Linkage analysis of large otosclerosis families has led to the identification of seven loci, and recently evidence was found that T cell receptor beta is a gene responsible for familial otosclerosis, suggesting an underlying immunological pathway. However, this might also represent an autoimmune process, a hypothesis that is supported by other data as well. In conclusion, a variety of pathways have been identified to be involved in the development of otosclerosis, showing that distinct mechanisms involving both genetic and environmental risk factors can influence and contribute to a similar disease outcome.

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Relation Between Renin-Angiotensin-Aldosterone System and Otosclerosis

Abstract: These observations suggest a relation between the local renin angiotensin system activity and otosclerosis, opening new therapeutic insights.

Cited by 39 publications

References 25 publications

Differences in gene expression between the otic capsule and other bones

Differences in gene expression between the otic capsule and other bones

COL1A1 association and otosclerosis: A meta‐analysis

The etiology of otosclerosis: A combination of genes and environment

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