title: Polymorphisms in KCNE1 or KCNE3 are not associated with Ménière disease in the Caucasian population.
abstract: Ménière disease (MD) is a complex disorder of unknown etiology characterized by the symptom triad of vertigo, sensorineural hearing loss, and tinnitus. Its reported incidence is 1-2 per 1,000 in Caucasians and 0.03-0.37 per 1,000 in Japanese. Doi et al. [Doi et al. (2005); ORL J Otorhinolaryngol Relat Spec 67:289-293] recently reported that two single nucleotide polymorphisms (SNPs) in KCNE1 and KCNE3 are associated with MD in Japanese subjects. Consistent with this possibility, these two genes encode potassium channels that are expressed in the stria vascularis and endolymphatic sac, respectively, and their role in ion transport suggests that they may be important in inner ear homeostasis. To establish whether a similar association exists in the Caucasian MD population, we sequenced the coding regions and exon-intron boundaries of both genes in 180 Caucasian persons with MD and 180 matched Caucasian controls. Neither of the two reported SNPs was significantly associated with MD when compared to the Caucasian controls (KCNE1, P = 0.55; KCNE3, P = 0.870). Comparison of allele frequencies between the Japanese MD population and our study population revealed no significant difference between groups (KCNE1, P = 0.90; KCNE3, P = 0.862), suggesting that the significant differences reported in the Japanese study arose from their control population. Six additional SNPs in both KCNE1 and KCNE3 were genotyped and none was associated with MD. Population stratification within our MD and Caucasian control population was excluded. Our data show that SNPs in KCNE1 and KCNE3 are not associated with MD in Caucasians.
authors.affiliation: Molecular Otolaryngology Research Laboratories, Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Campbell
authors.forename: Charley C
authors.initials: CC
authors.lastname: Della Santina
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Meyer
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Smith
authors.forename: Oluwaseun A
authors.initials: OA
authors.lastname: Myrie
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Kuni
authors.initials: K
authors.lastname: Fukushima
authors.forename: Joseph
authors.initials: J
authors.lastname: Califano
authors.forename: John P
authors.initials: JP
authors.lastname: Carey
authors.forename: Marlan R
authors.initials: MR
authors.lastname: Hansen
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Gantz
authors.forename: Lloyd B
authors.initials: LB
authors.lastname: Minor
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008575:Meniere Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D044465:White People
chemical_list: C489622:KCNE1 protein, human; C418492:KCNE3 protein, human; D024642:Potassium Channels, Voltage-Gated