No evidence for association between the renin-angiotensin-aldosterone system and otosclerosis in a large Belgian-Dutch population.

Contains fulltext : 81265.pdf (publisher's version ) (Closed access)HYPOTHESIS/BACKGROUND: Otosclerosis is a frequent cause of hearing impairment in the Caucasian population and is characterized by abnormal bone remodeling of the otic capsule. Associations with several genes have been reported, and recently, an association between the renin-angiotensin-aldosterone system and otosclerosis has been suggested. Polymorphisms in 3 genes were investigated: angiotensinogen (AGT), angiotensin I-converting enzyme (ACE), and angiotensin II receptor, type 1. The polymorphisms in AGT and ACE were associated with disease, and both were reported to interact with each other. In the current study, a replication study was done in a large Belgian-Dutch population to investigate whether this association could be replicated. METHODS: The same 3 polymorphisms in AGT, ACE, and angiotensin II receptor, type 1 as analyzed in the original study were investigated in 692 otosclerosis patients and 692 controls of Belgian-Dutch origin. RESULTS: None of the polymorphisms were significantly associated with disease. Interaction between AGT and ACE polymorphisms was not significant either. CONCLUSION: We could not confirm the association between AGT and ACE, nor could we find evidence for interaction between both genes in otosclerosis. Because the current patient set is much larger than the one from the original study, this study holds sufficient power to detect the previously reported associations. Nonreplication in this case probably indicates that the initial results were false positive, although a role for these genes in otosclerosis cannot be definitively ruled out

A European multicenter study into age-related hearing impairment: Occupational noise, smoking and high BMI are risk factors and moderate akcohol consumption is protective.

Contains fulltext : 70695.pdf (publisher's version ) (Closed access

The contribution of GJB2 (Connexin 26) 35delG to age-related hearing impairment and noise-induced hearing loss.

Contains fulltext : 52415.pdf (publisher's version ) (Closed access)HYPOTHESIS: The common GJB2 (Connexin 26) 35delG mutation might contribute to the development of age-related hearing impairment (ARHI) and noise-induced hearing loss (NIHL). BACKGROUND: GJB2, a gene encoding a gap junction protein expressed in the inner ear, has been suggested to be involved in the potassium recycling pathway in the cochlea. GJB2 mutations account for a large number of individuals with nonsyndromic recessive hearing loss, with 35delG being the most frequent mutation in populations of European origin. Other genes involved in potassium homeostasis have been suggested to be associated with ARHI and NIHL, and distortion product otoacoustic emission distortions indicative of hearing loss alterations have been found in 35delG carriers. METHOD: We genotyped 35delG in two distinct sample sets: an ARHI sample set, composed of 2,311 Caucasian samples from nine different centers originating from seven different countries with an age range between 53 and 67 years, and an NIHL sample set consisting of 702 samples from the two extremes of a noise-exposed Polish sample. RESULTS: After statistical analysis, we were unable to detect an association between 35delG and ARHI, nor between 35delG and NIHL. CONCLUSION: Our findings indicate that there is no increased susceptibility in 35delG carriers for the development of ARHI or NIHL