title: KCNQ4: a gene for age-related hearing impairment?
abstract: Age-related hearing impairment (ARHI) is the most common sensory impairment among the elderly. It is a complex disorder influenced by genetic as well as environmental factors. SNPs in a candidate susceptibility gene, KCNQ4, were examined in two independent Caucasian populations. Two quantitative trait locus (QTL) values were investigated: Zhigh and Zlow, a measure of high and respectively low frequency hearing loss. In the first population, the statistical analysis of 23 genotyped SNPs spread across KCNQ4 resulted in significant p-values for two SNPs for Zhigh-SNP9 (NT_004511:g.11244177A > T) and SNP15 (NT_004511:g.11257005C > T; NP_004691:p.Ala259Ala), and one SNP for Zlow-SNP12 (NT_004511:g.11249550A > T). The linkage disequilibrium (LD) structure of KCNQ4 was subsequently determined in a 34-kb region surrounding the significant SNPs, resulting in three LD-blocks. LD-block 1 contains SNP9 and covers an area of 5 kb, LD-block 2 measures 5 kb and surrounds SNP13 (NT_004511:g.11253513A > G) to SNP18 (NT_004511:g.11257509G > A; NP_004691:p.Thr293Thr), and LD-block 3 spans 7 kb. Five tag-SNPs of block 1 and 2, and 2 extra SNPs were subsequently genotyped in the second population. Again, several SNPs were positively associated with ARHI: one SNP (SNP18) for the high frequencies and three SNPs (SNP9, SNP12, and SNP18) for the low frequencies, although only a single SNP (SNP12) resulted in significant p-values in both populations. Nevertheless, the associated SNPs of both populations were all located in the same 13-kb region in the middle of the KCNQ4 gene.
authors.affiliation: Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Van Eyken
authors.forename: L
authors.initials: L
authors.lastname: Van Laer
authors.forename: E
authors.initials: E
authors.lastname: Fransen
authors.forename: V
authors.initials: V
authors.lastname: Topsakal
authors.forename: N
authors.initials: N
authors.lastname: Lemkens
authors.forename: W
authors.initials: W
authors.lastname: Laureys
authors.forename: N
authors.initials: N
authors.lastname: Nelissen
authors.forename: A
authors.initials: A
authors.lastname: Vandevelde
authors.forename: T
authors.initials: T
authors.lastname: Wienker
authors.forename: P
authors.initials: P
authors.lastname: Van De Heyning
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D000328:Adult; D000367:Age Factors; D000369:Aged, 80 and over; D000704:Analysis of Variance; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051656:KCNQ Potassium Channels / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics
chemical_list: D051656:KCNQ Potassium Channels; C117367:KCNQ4 protein, human