Variations in HSP70 genes associated with noise-induced hearing loss in two independent populations

Abstract

Noise-induced hearing loss (NIHL) is one of the most important occupational health hazards. Millions of people worldwide are exposed daily to harmful levels of noise. NIHL is a complex disease resulting from an interaction between genetic and environmental factors. Although the environmental risk factors have been studied extensively, little is known about the genetic factors. Heat-shock proteins (HSPs) are induced after exposure to severe noise. When first induced by exposure to moderate sound levels, they can protect the ear from damage from excessive noise exposure. This protection is highly variable between individuals. An association of HSP70 genes with NIHL has been described by Yang et al (2006) in a Chinese sample set of noise-exposed workers. In this study, three polymorphisms (rs1043618, rs1061581 and rs2227956) in HSP70-1, HSP70-2 and HSP70-hom, respectively, were genotyped in 206 Swedish and 238 Polish DNA samples of noise-exposed subjects and analyzed. One SNP, rs2227956 in HSP70-hom, resulted in a significant association with NIHL in both sample sets. In addition, rs1043618 and rs1061581 were significant in the Swedish sample set. Analysis of the haplotypes composed of the three SNPs revealed significant associations between NIHL and haplotype GAC in both sample sets and with haplotype CGT in the Swedish sample set. In conclusion, this study replicated the association of HSP70 genes with NIHL in a second and third independent noise-exposed sample set, hereby adding to the evidence that HSP70 genes may be NIHL susceptibility genes.

HLA complex-linked heat shock protein genes and childhood acute lymphoblastic leukemia susceptibility

“…1b). This finding corroborates with a recent report that used the same three SNPs in an association study in two European populations (Konings et al 2009) and another report which used three SNPs from the same genes with one SNP being different (Singh et al 2006b). LD plots in the control groups are shown in Fig.…”

“…There are numerous associations with HSPA1A/B/L SNPs in many diseases most of which with successful replications (Favatier et al 1997;Temple et al 2004;Singh et al 2006a, b;Kee et al 2008;Jeng et al 2008;Shibata et al 2009;Konings et al 2009). This is in agreement with pleiotropic functions of HSPs.…”

A Protein Interaction Network for the Large Conductance Ca2+-activated K+ Channel in the Mouse Cochlea

“…Although, the mechanism for this result is not understood, our HSP60 data provide possible links to this discovery. HSPs are associated with NIHL in humans (69), increase in response to acoustic overstimulation (70), and protect the cochlea from noise damage (71). In contrast to the outcome with calreticulin and GRP78, silencing of HSP60, in our study, resulted in an increase in BK expression.…”

Deaf mute or Deaf

“…One in 500 new borns has bilateral permanent sensorineural hearing loss ≥40 dB; and by adolescence, it becomes to 3.5 per 1000 (Morton et al, 2006;Konings et al, 2009). In US congenital SNHL occurs about three times more common than Down's syndrome (Gorlin et al, 1995).…”

“…Acquired hearing loss in adults is most often caused by environmental factors but mainly due to environmental-genetic interactions. Age-related and noiseinduced hearing losses are the most frequent examples of complex ‗environmental-genetic' hearing loss; but, up till now only a few genes have been associated with these complex traits (Konings et al, 2009). Aminoglycoside-induced hearing loss is more common in persons with an A-to-G transition at nucleotide position 1555 in the mitochondrial genome (mtDNA) (Nance, 2003).…”