[Genetic factors in susceptibility to age- and noise-related hearing loss].
Individual susceptibility to age-related hearing loss (AHL) and noise-induced hearing loss (NIHL) varies greatly, and this inter-individual variation is due to an interaction of environmental factors, individual factors, and susceptibility genes. Majority of studies on susceptibility genes for AHL and NIHL have been performed in mice model. These findings suggest the role of the same genes in the development of AHL and NIHL, the more so as the pathogenesis of both diseases is similar with a crucial role of oxidative stress. The alleles responsible for AHL have been localized to the chromosome 10 (Ahl gene). Ahl-/- mice develop hearing impairment at early age and are also oversensitive to noise. Ahl gene is a recessive gene and it is probably responsible for the synthesis of cell junction proteins. In mice ahl codes for cadherin (CDH) proteins. The cadherin of interest is named otocadherin or CDH23, and it is localized to the links between stereocilia of hair cells. A hypomorphic 753G>A single nucleotide polymorphism (SNP) in Cdh 23 is associated with AHL, and the 753A variant is also correlated with susceptibility to NIHL. An increased susceptibility to AHL and NIHL may rely on the SNPs of several other genes, including the groups of oxidative stress genes, K+ ions recycling genes, monogenic deafness genes (including Connexin 26 gene, which mutation is responsible for the most frequent hereditary deafness in Caucasians), as well as mitochondrial genes. Several oxidative stress enzyme (sod1-/-, gpx -/-) knock-out mice have been shown to be more susceptible to NIHL than wild strains. Current large-scale cohort studies on AHL and NIHL performed under the European projects in between-lab collaboration along with a dynamic progress in the field of genetics of deafness open up new opportunities to find human AHL and NIHL susceptibility genes and develop methods for AHUNIHL treatment.
Sliwińiska-Kowalska
Mariola
M
Institut Medycyny Pracy w łodzi, Klinika Audiologii i Foniatrii oraz Zakład ZagroZeń Fizycznych. marsliw@imp.lodz.pl
Pawelczyk
Małgorzata
M
Kowalski
Tomasz Jarema
TJ
D000368:Aged; D000375:Aging / Q000235:genetics*; D000818:Animals; D020022:Genetic Predisposition to Disease; D006317:Hearing Loss, Noise-Induced / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009623:Noise, Occupational / Q000009:adverse effects