Age-Related Hearing Impairment (ARHI) is one of the frequent sensory disorders registered in 50% of individuals over 80 years. ARHI is a multifactorial disorder due to environmental and poor-known genetic components. In this study, we present the data on age-related hearing impairment of 48 heterozygous carriers of mutation IVS1+1G>A (GJB2 gene) and 97 subjects with GJB2 genotype wt/wt in the Republic of Sakha/Yakutia (Eastern Siberia, Russia). This subarctic territory was found as the region with the most extensive accumulation of mutation IVS1+1G>A in the world as a result of founder effect in the unique Yakut population isolate. The GJB2 gene resequencing and detailed audiological analysis in the frequency range 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 kHz were performed in all examined subjects that allowed to investigate genotype-phenotype correlations between the presence of single mutation IVS1+1G>A and hearing of subjects from examined groups. We revealed the linear correlation between increase of average hearing thresholds at speech frequencies (PTA0.5,1.0,2.0,4.0 kHz) and age of individuals with GJB2 genotype IVS1+1G>A/wt (rs?=?0.499, p?=?0.006860 for males and rs?=?0.427, p?=?0.000277 for females). Moreover, the average hearing thresholds on high frequency (8.0 kHz) in individuals with genotype IVS1+1G>A/wt (both sexes) were significantly worse than in individuals with genotype wt/wt (pA/wt was estimated to be ~40 years (rs?=?0.504, p?=?0.003). These findings demonstrate that the single IVS1+1G>A mutation (GJB2) is associated with age-related hearing impairment (ARHI) of the IVS1+1G>A carriers in the Yakuts.
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Cites: Brain Res Brain Res Rev. 2000 Apr;32(1):159-6210928803
Cites: Hear Res. 2013 Sep;303:30-823422312
Cites: Hear Res. 2003 Jan;175(1-2):140-5112527132
Cites: Ann N Y Acad Sci. 1991;630:16-311952587
Cites: Nature. 1997 May 1;387(6628):80-39139825
Cites: Am J Hum Genet. 1997 May;60(5):1174-839150165
Cites: Hum Mol Genet. 1997 Sep;6(9):1605-99285800
Cites: Am J Hum Genet. 1998 Apr;62(4):792-99529365
Cites: N Engl J Med. 1998 Nov 19;339(21):1500-59819448
Cites: Lancet. 2005 Mar 5-11;365(9462):879-9015752533