Molecular analysis of aquaporin genes 1 to 4 in patients with Menière's disease

Background: Menière's Disease (MD) is an episodic cochleovestibular dysfunction of unknown etiology, still lacking a specific test and therapy. The proposed theories on the pathophysiology include genetic factors and factors relating to inner ear homeostasis. Various aquaporins (AQP), water channels, expressed in the inner ear and the vestibular organ, are involved in homeostasis. Mutations in AQP genes could result in disturbed inner ear homeostasis and endolymphatic hydrops, and therefore be involved in the pathogenesis of MD.

Aim: To search for mutations in AQP1 to 4 in patients suffering from MD.

Methods: In patients with definite MD, DNA was extracted from whole blood. The coding sequences of AQP1 to 4 were amplified by PCR reaction and sequenced.

Results: One sequence alteration, homozygous c.105G->C (conservative change without alteration of amino acid) in AQP3 was detected in 11 out of 34 patients but not in 100 control chromosomes.

Conclusion: By itself the detected alteration is unlikely to play a role in the pathogenesis of MD. However, together with an additional modifying gene an effect can not be excluded. Additional regions (introns, splice-sites) and other genes involved in inner ear homeostasis need to be analyzed to identify a possible molecular alteration in MD.