Age-Related Hearing Impairment 2

Description

Age-related hearing impairment (ARHI), or presbycusis, is the progressive, bilaterally symmetric deterioration of hearing ability that occurs with aging. Studies of the cochlea in many animal species and of the histopathology of human temporal bones have shown that stria vascularis volumes and spiral ganglion cell, inner hair cell, and outer hair cell populations, as well as many other cochlear cell types and structures, undergo age-related degeneration. Environmental risk factors for ARHI include noise exposure, smoking, ototoxic medication, and cardiovascular disease. Heritability estimates vary between 0.25 and 0.75 depending on, among other factors, study design (family vs twins), age range of the study population, and the phenotype studied (Huyghe et al., 2008).

Mapping

Friedman et al. (2009) conducted a pooling-based genomewide association study of ARHI. DNA pools for cases and controls were allelotyped on a 500K microarray for each center separately. Top-ranked SNPs were genotyped in 846 individuals with ARHI and 846 controls selected from 3,434 individuals in 6 European countries. In 1,332 non-Finnish European individuals, the authors found a significant association between ARHI and rs11928865 within the GRM7 gene (604101) on chromosome 3p26.1-p25.1, which was replicated in 130 non-Finnish Europeans. In 360 Finnish individuals, rs779706 and rs779701 in the GRM7 gene showed significant association. These latter SNPs could not be replicated in the European group, nor could rs11928865 be replicated in the Finnish group, suggesting the signals were independent of each other. Combined analysis of all groups for rs11928865 yielded a p value of 9.0 x 10(-5). Friedman et al. (2009) noted that the European and Finnish association signals were approximately 300 kb apart, which could possibly be the result of allelic heterogeneity or smaller effect size.

In a genomewide association study of age-related hearing impairment involving 347 Finnish Saami individuals aged 50 to 70 years, Van Laer et al. (2010) found significant association to rs161927 (p = 0.000149), which is downstream of the GRM7 gene, but did not confirm association of rs11928865 (p = 0.045) reported previously by Friedman et al. (2009). Van Laer et al. (2010) also identified significant association to an intronic SNP rs457717 (p = 3.55 x 10(-7)) in the IQGAP2 gene (605401) on chromosome 5q11-q13.