title: The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss.
abstract: Noise-induced hearing loss (NIHL) is one of the most important occupational diseases and, after presbyacusis, the most frequent cause of hearing loss. NIHL is a complex disease caused by an interaction between environmental and genetic factors. The various environmental factors involved in NIHL have been relatively extensively studied. On the other hand, little research has been performed on the genetic factors responsible for NIHL. To test whether the variation in genes involved in coupling of cells and potassium recycling in the inner ear might partly explain the variability in susceptibility to noise, we performed a case-control association study using 35 SNPs selected in 10 candidate genes on a total of 218 samples selected from a population of 1,261 Swedish male noise-exposed workers. We have obtained significant differences between susceptible and resistant individuals for the allele, genotype, and haplotype frequencies for three SNPs of the KCNE1 gene, and for the allele frequencies for one SNP of KCNQ1 and one SNP of KCNQ4. Patch-clamp experiments in high K+-concentrations using a Chinese hamster ovary (CHO) cell model were performed to investigate the possibility that the KCNE1-p.85N variant (NT_011512.10:g.21483550G>A; NP_00210.2:p.Asp85Asn) was causative for high noise susceptibility. The normalized current density generated by KCNQ1/KCNE1-p.85N channels, thus containing the susceptibility variant, differed significantly from that from wild-type channels. Furthermore, the midpoint potential of KCNQ1/KCNE1-p.85N channels (i.e., the voltage at which 50% of the channels are open) differed from that of wild-type channels. Further genetic and physiological studies will be necessary to confirm these findings.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium. Lut.VanLaer@ua.ac.be
authors.forename: Lut
authors.initials: L
authors.lastname: Van Laer
authors.forename: Per-Inge
authors.initials: PI
authors.lastname: Carlsson
authors.forename: Natacha
authors.initials: N
authors.lastname: Ottschytsch
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Bondeson
authors.forename: Annelies
authors.initials: A
authors.lastname: Konings
authors.forename: Ann
authors.initials: A
authors.lastname: Vandevelde
authors.forename: Nele
authors.initials: N
authors.lastname: Dieltjens
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.forename: Dirk
authors.initials: D
authors.lastname: Snyders
authors.forename: Erik
authors.initials: E
authors.lastname: Borg
authors.forename: Adam
authors.initials: A
authors.lastname: Raes
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D007758:Ear, Inner / Q000378:metabolism*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006317:Hearing Loss, Noise-Induced / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051656:KCNQ Potassium Channels / Q000235:genetics; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D009623:Noise, Occupational; D018408:Patch-Clamp Techniques; D020641:Polymorphism, Single Nucleotide; D011188:Potassium / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*
chemical_list: C489622:KCNE1 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C117367:KCNQ4 protein, human; D024642:Potassium Channels, Voltage-Gated; D011188:Potassium