title: Age-Related Hearing Impairment (ARHI) associated with GJB2 single mutation IVS1+1G>A in the Yakut population isolate in Eastern Siberia.
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.
authors: Department of Molecular Genetics, Yakut Scientific Centre of Complex Medical Problems, Siberian Branch of the Russian Academy of Medical Sciences, Yakutsk, Russian Federation; Laboratory of Molecular Biology, Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Nikolay A
authors: NA
authors: Barashkov
authors: Department of Molecular Genetics, Yakut Scientific Centre of Complex Medical Problems, Siberian Branch of the Russian Academy of Medical Sciences, Yakutsk, Russian Federation; Laboratory of Molecular Biology, Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Fedor M
authors: FM
authors: Teryutin
authors: Department of Molecular Genetics, Yakut Scientific Centre of Complex Medical Problems, Siberian Branch of the Russian Academy of Medical Sciences, Yakutsk, Russian Federation.
authors: Vera G
authors: VG
authors: Pshennikova
authors: Laboratory of Molecular Biology, Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Aisen V
authors: AV
authors: Solovyev
authors: Department of Radiology, Republican Hospital #2- Center of Emergency Medicine, Ministry of Public Health of the Sakha Republic, Yakutsk, Russian Federation.
authors: Leonid A
authors: LA
authors: Klarov
authors: Department of Molecular Genetics, Yakut Scientific Centre of Complex Medical Problems, Siberian Branch of the Russian Academy of Medical Sciences, Yakutsk, Russian Federation.
authors: Natalya A
authors: NA
authors: Solovyeva
authors: Republican Centre of Professional Pathology, Republican Hospital #2- Center of Emergency Medicine, Ministry of Public Health of the Sakha Republic, Yakutsk, Russian Federation.
authors: Andrei A
authors: AA
authors: Kozhevnikov
authors: Audiology-Logopaedic Center, Republican Hospital #1- National Medical Centre, Ministry of Public Health of the Sakha Republic, Yakutsk, Russian Federation.
authors: Lena M
authors: LM
authors: Vasilyeva
authors: Audiology-Logopaedic Center, Republican Hospital #1- National Medical Centre, Ministry of Public Health of the Sakha Republic, Yakutsk, Russian Federation.
authors: Elvira E
authors: EE
authors: Fedotova
authors: Department of Pediatric, Medical Institute, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Maria V
authors: MV
authors: Pak
authors: Department of Normal and Abnormal Anatomy, Operative Surgery with Topographic Anatomy and Forensic Medicine, Medical Institute, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Sargylana N
authors: SN
authors: Lekhanova
authors: Institute of Foreign Philology and Regional Studies, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Elena V
authors: EV
authors: Zakharova
authors: Laboratory of Molecular Biology, Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation; Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Kyunney E
authors: KE
authors: Savvinova
authors: Laboratory of Molecular Biology, Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation; Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Nyurgun N
authors: NN
authors: Gotovtsev
authors: Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Adyum M
authors: AM
authors: Rafailo
authors: Department of Radiology, Republican Hospital #2- Center of Emergency Medicine, Ministry of Public Health of the Sakha Republic, Yakutsk, Russian Federation.
authors: Nikolay V
authors: NV
authors: Luginov
authors: Institute of Humanitarian Research and Indigenous Peoples of the North, Siberian Branch of the Russian Academy of Sciences, Yakutsk, Russian Federation.
authors: Anatoliy N
authors: AN
authors: Alexeev
authors: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation; Novosibirsk State University, Novosibirsk, Russian Federation.
authors: Olga L
authors: OL
authors: Posukh
authors: Department of Genomics, Institute of Biochemistry and Genetics, Ufa Scientific Centre, Russian Academy of Sciences, Ufa, Russian Federation.
authors: Lilya U
authors: LU
authors: Dzhemileva
authors: Department of Genomics, Institute of Biochemistry and Genetics, Ufa Scientific Centre, Russian Academy of Sciences, Ufa, Russian Federation; Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russian Federation.
authors: Elza K
authors: EK
authors: Khusnutdinova
authors: Department of Molecular Genetics, Yakut Scientific Centre of Complex Medical Problems, Siberian Branch of the Russian Academy of Medical Sciences, Yakutsk, Russian Federation; Laboratory of Molecular Biology, Institute of Natural Sciences, M.K. Ammosov North-Eastern Federal University, Yakutsk, Russian Federation.
authors: Sardana A
authors: SA
authors: Fedorova
mesh_terms: D000367:Age Factors; D044466:Asian People / Q000235:genetics; D000072259:Connexin 26; D017630:Connexins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D004252:DNA Mutational Analysis; D018703:Founder Effect; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D009154:Mutation; D012800:Siberia
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26