Gly460Trp α-Adducin Mutation as a Possible Mechanism Leading to Endolymphatic Hydrops in Ménière's Syndrome

Abstract

Ménière's disease (MD) is an inner ear disorder characterized by recurrent episodic vertigo, hearing loss that is fluctuating in the first stages, aural fullness, and tinnitus. Raised endolymphatic pressure (hydrops) is commonly accepted as a causal condition. Approximately 90% of cases of MD are sporadic, whereas the remaining 10% of cases are linked to genetic factors. The ionic composition of endolymph may also depend on the activity of Na, K-ATPase. Adducin is a heterodimeric cytoskeleton protein consisting of 3 subunits (alpha, beta, and gamma) coded by 3 different genes (ADD1, ADD2, and ADD3). ADD1 Gly460Trp polymorphism is associated with salt-sensitive hypertension and increased Na-K pump activity in transfected cells. This study aims to verify the role of adducin in the development of MD. We genotyped 28 patients affected by definite MD according to American Academy of Otolaryngology-Head and Neck Surgery Foundation criteria. Results were compared with those from 2 different control populations (normotensive control group from San Raffaele Hospital and general population group). We have not found any significant difference in the distribution of ADD2 C1797T and ADD3 IVS11+386A/G polymorphism genotypes. On the other hand, the frequency of ADD1 Trp allele is significantly increased in patients with MD compared with controls. We present data supporting the possibility that increased Na, K-ATPase activity may be one of the pathologic mechanisms inducing hyperosmolarity in endolymph which, in turn, may lead to hydrops.