A replication study on proposed candidate genes in Ménière's disease, and a review of the current status of genetic studies

Abstract

Objective: Multiple candidate genes have been presented for Ménière's disease (MD), but to date no positive replications have been reported. We review here all the previously proposed candidate genes for MD and report our results on the analysis of six such genes, AQP2, KCNE1, KCNE3, HCFC1, COCH, and ADD1. Study sample: A well-defined sample set of 38 sporadic and 21 familial Finnish MD patients. Design: Mutation analysis, case-control study, and review of literature. Results: A polymorphism rs1805127 in the potassium channel gene, KCNE1, was associated with MD in sporadic (p = 0.011), but not familial patients (p = 0.62). In addition, we identified four novel unique variations in the KCNE1 gene. PolyPhen and Mutation Taster analyses indicated that at least one of the variations c.259T > C; p.Trp87Arg is probably damaging to the coded protein. Conclusions: Our review of the reported candidate genes shows that the current understanding of the genetic factors contributing to the development of MD is limited, and that the study of its etiology would benefit greatly from more comprehensive genetic knowledge.

Key Words::

• Ménière's disease
• genetics
• candidate gene
• KCNE1
• sporadic
• familial

Acknowledgements

The study was supported by the Finnish Foundation for Ear Diseases and the Emil Aaltonen Foundation. We wish to thank the patients for their participation, and Aira Erkkilä and Helena Satulehto for their excellent technical assistance.

Declaration of interest: The authors declare that there are no conflicts of interest.