title: 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.
  
  
  METHODS
  A well-defined sample set of 38 sporadic and 21 familial Finnish MD patients.
  
  
  METHODS
  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.
authors.affiliation: Oulu Center for Cell-Matrix Research, Biocenter and Department of Medical Biochemistry and Molecular Biology, Institute of Biomedicine, University of Oulu, Finland. elina.hietikko@oulu.fi
authors.forename: Elina
authors.initials: E
authors.lastname: Hietikko
authors.forename: Jouko
authors.initials: J
authors.lastname: Kotimäki
authors.forename: Annaleena
authors.initials: A
authors.lastname: Okuloff
authors.forename: Martti
authors.initials: M
authors.lastname: Sorri
authors.forename: Minna
authors.initials: M
authors.lastname: Männikkö
mesh_terms: D051399:Aquaporin 2 / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005838:Genotype; D051863:Host Cell Factor C1 / Q000235:genetics; D006801:Humans; D008575:Meniere Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D000099291:Adducins
chemical_list: D051399:Aquaporin 2; D002148:Calmodulin-Binding Proteins; D016326:Extracellular Matrix Proteins; D051863:Host Cell Factor C1; D024642:Potassium Channels, Voltage-Gated; D000099291:Adducins; C110668:COCH protein, human; C497692:HCFC1 protein, human; C489622:KCNE1 protein, human; C418492:KCNE3 protein, human