Endolymphatic hydrops and ionic transporters: genetic and biohumoral aspects.

ABSTRACT

Ménière's disease (MD) is an inner ear disorder, characterized by a burden of symptoms, probably arising from the interplay of genetic and environmental factors. In this brief review, we consider the role of ion channels and transporters in the pathophysiology of MD, focusing on genetic and biohumoral aspects. Pathophysiological mechanisms related to altered concentrations of ions in the endolymph include altered osmotic pressure leading to hydrops and/or immunomodulatory effects of K+ and Endogenous Ouabain (EO) concentrations in the inner ear. Aquaporins 1-5 (AQPs) have been found in the inner ear; AQP2 is the only isoform controlled by a hormone, namely, vasopressin (antidiuretic hormone, ADH). Genetic studies on AQPs have provided inconclusive results. Recently, two genetic polymorphisms have been associated with MD rs3746951, a missense variant (Gly180Ser) in the Salt-Inducible Kinase-1 (SIK1) gene and rs487119, an intronic variant of gene SLC8A1 coding for a Na+,Ca++ exchanger (NCX-1). EO is a hormone released by the midbrain and adrenal glands. It controls the constitutive capacity of modulating Na+,K+-ATPase activity. Higher plasma levels of EO have been found in MD subjects compared to a control group.