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.

A genome-wide association study for age-related hearing impairment in the Saami

“…Intriguingly, the SNP rs161927 (P-value 0.000149), that ranked eighth for PC1, was positioned immediately downstream from the metabotropic GRM7 gene. A previous GWAS of a European and a Finnish sample set, which was based on an age-and gendercorrected Z-score highly correlated with our PC1, 9,11,28,42 already suggested a role for GRM7 in ARHI. 9 GRM7 encodes a metabotropic glutamate receptor that can be activated by L-glutamate, the primary excitatory neurotransmitter in the cochlear hair cell.…”

“…Except for the age range that was used, the ARHI selection criteria were as described previously. 28 Briefly, all volunteers completed an extended questionnaire detailing medical history and exposure to environmental factors putatively influencing hearing. Subjects suffering from one or more medical pathologies from a standardised list of conditions that could potentially affect hearing ability were excluded.…”

DTI Analysis of Presbycusis Using Voxel-Based Analysis

“…The complete list of exclusion criteria was previously described. 13 Fourteen age-and sex-matched healthy controls (control group, 6 men and 8 women; mean age, 62.4 Ϯ 2.0 years; PTA Յ25 dB HL in the better-hearing ear) were recruited for this study. All controls were in good health and had no history of neurologic or psychiatric disease.…”

Analysis of inner ear potassium recycling genes as potential factors associated with tinnitus

“…Among them 33 SNPs were genotyped with AcycloPrime Fluorescence Polarization (FP) SNP Detection System (Perkin Elmer Life Sciences, Boston, MA, USA) as described before [19]. SNPs, for which no assay could be developed with the FP methods, were genotyped with the SNaPshot detection system (Applied Biosystems, Foster City, CA, USA), as described previously [24]. Additionally 66 SNPs were genotyped by Illumina.…”