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

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.