Single nucleotide polymorphisms in the cadherin 23 (CDH23) gene in Polish workers exposed to industrial noise

Abstract

Single nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome and may underlie differential susceptibility to common genetic diseases. A candidate gene for susceptibility to noise-induced hearing loss (NIHL) is Cadherin 23 (CDH23). This study aimed to analyze genetic variation in the CDH23 gene in a group of 10 individuals derived from a cohort of 949 workers exposed to noise, and consisted of five persons from each of the resistant and susceptible extremes. DNA samples were collected and the coding exons of CDH23 were sequenced. We identified a total of 35 SNPs: 11 amino acid substitutions, 8 silent nucleotide changes, and 16 substitutions in intervening sequences. Ten of the 11 amino acid substitutions were previously shown also to segregate in a Cuban population. The nonsynonymous SNPs localized to the part of the gene encoding the extracellular domain of Cadherin 23, in particular ectodomains 5, 13, 14, 15, 16, 17, 19, and 22. One amino acid change occurred at a conserved position in ectodomain 5. Our results provide a framework for future study of polymorphisms in CDH23 as risk factor for NIHL.

A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells

“…An interesting implication of our findings is that some CDH23 mutations may predispose individuals to hearing loss caused by mechanical insults. In fact, polymorphisms in CDH23 are associated with noise-induced hearing loss (43), and mice heterozygous for the Cdh23 waltzer allele show increased noise susceptibility (44). Finally, a polymorphism in Cdh23 is associated with age-related hearing loss (14), which may be related to instability of tip links.…”

Feasibility of a bilateral 4000–6000 Hz notch as a phenotype for genetic association analysis

“…These include a variety of metabolic enzymes and heat shock proteins tied to redox regulation (Yang, et al, 2006; Konings, et al 2007; Lin, et al, 2010; Liu, et al, 2010a, b; Abreu-Silva, et al, 2011), ion channels and ion transport proteins, and structural and gap junction proteins (Van Laer, et al, 2006; Konings, et al, 2007; Slwinska-Kowalska, et al, 2008; Pawelczyk, et al, 2009). , These findings have been replicated for catalase (CAT) the heat shock protein HSP70, potassium ion channels (KCNQ4, KCNE1), myosin 14 (MYO14) and protocadherin 15 (PCDH15).…”

Noise induced hearing loss: Research in central, eastern and south-eastern Europe and newly independent states

“…[65][66][67][68] For example, Pawełczyk et al, [66] suggested a possible role of potassium-recycling pathway genes in determining the individual susceptibility to NIHL. Another candidate gene for NIHL susceptibility is cadherin 23 (CDH23), which is a component of the inter-stereocilia links on the cochlear hair cells.…”

“…Another candidate gene for NIHL susceptibility is cadherin 23 (CDH23), which is a component of the inter-stereocilia links on the cochlear hair cells. [65] In the Nofer Institute of Occupational Medicine, Lodz, Poland, apart of human studies, animal research had been performed in the past on guinea pig, chick, and mouse models under the leadership of Mariola Śliwińska-Kowalska. The morphological changes in the guinea pig's cochlea examined after exposures to noise using the light and electron microscopy were described.…”