Age-Related Hearing Impairment (ARHI) associated with GJB2 single mutation IVS1+1G>A in the Yakut population isolate in Eastern Siberia

PLoS One. 2014 Jun 24;9(6):e100848. doi: 10.1371/journal.pone.0100848. eCollection 2014.

Abstract

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 (p<0.05). Age of hearing loss manifestation in individuals with genotype IVS1+1G>A/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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Asian People / genetics
  • Connexin 26
  • Connexins / chemistry
  • Connexins / genetics*
  • Connexins / physiology
  • DNA Mutational Analysis
  • Founder Effect
  • Hearing Loss / genetics*
  • Humans
  • Mutation*
  • Siberia

Substances

  • Connexins
  • GJB2 protein, human
  • Connexin 26

Grants and funding

The authors thank all patients and blood sample donors who have contributed to this study. This study was supported by the Russian Foundation for Basic Research (12-04-00342_a, 12-04-98520_r_vostok_a, 12-04-97004_r_povolzhye_a, 12-04-31230_mol_a, 14-04-01741_A), Federal Program «Scientific and educational staff for innovative Russia» (#16.740.11.0190, #16.740.11.0346), Integration project of SB RAS #92 «Ethnogeny of indigenous peoples in Siberia and North Asia: comparative, historical, ethno-social and genomic analysis», the Sakha Republic President Grant#80 for Young Researchers for 2014 year, Scientific and Educational Foundation for Young Scientists of Republic of Sakha (Yakutia) for 2014 year, Project #656 of Ministry of Education and Science of Russia, by grant #30 (2013–2015) of RAS Program «Fundamental Sciences for Medicine». The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.