Barashkov Nikolay A, Teryutin Fedor M, Pshennikova Vera G, Solovyev Aisen V, Klarov Leonid A, Solovyeva Natalya A, Kozhevnikov Andrei A, Vasilyeva Lena M, Fedotova Elvira E, Pak Maria V, Lekhanova Sargylana N, Zakharova Elena V, Savvinova Kyunney E, Gotovtsev Nyurgun N, Rafailo Adyum M, Luginov Nikolay V, Alexeev Anatoliy N, Posukh Olga L, Dzhemileva Lilya U, Khusnutdinova Elza K, Fedorova Sardana A
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.
Department of Molecular Genetics, Yakut Scientific Centre of Complex Medical Problems, Siberian Branch of the Russian Academy of Medical Sciences, Yakutsk, Russian Federation.
PLoS One. 2014 Jun 24;9(6):e100848. doi: 10.1371/journal.pone.0100848. eCollection 2014.
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.
年龄相关性听力减退（ARHI）是一种常见的感觉障碍，在80岁以上的人群中，有50%的人患有该疾病。ARHI是一种由环境因素和尚不明确的遗传因素共同导致的多因素疾病。在本研究中，我们展示了在萨哈共和国/雅库特（俄罗斯东西伯利亚）的48名IVS1+1G>A（GJB2基因）突变杂合携带者以及97名GJB2基因型为wt/wt受试者的年龄相关性听力减退数据。由于雅库特独特人群隔离中的奠基者效应，这个亚北极地区被发现是世界上IVS1+1G>A突变积累最为广泛的地区。对所有受试对象进行了GJB2基因重测序，并在0.25、0.5、1.0、2.0、4.0、8.0 kHz频率范围内进行了详细的听力学分析，从而能够研究单一IVS1+1G>A突变的存在与受试组受试者听力之间的基因型-表型相关性。我们发现，GJB2基因型为IVS1+1G>A/wt的个体，其言语频率（PTA0.5、1.0、2.0、4.0 kHz）平均听力阈值的升高与年龄之间存在线性相关性（男性rs = 0.499，p = 0.006860；女性rs = 0.427，p = 0.000277）。此外，基因型为IVS1+1G>A/wt的个体（无论男女）在高频（8.0 kHz）的平均听力阈值显著低于基因型为wt/wt的个体（p<0.05）。基因型为IVS1+1G>A/wt的个体听力损失出现的年龄估计约为40岁（rs = 0.504，p = 0.003）。这些发现表明，单一的IVS1+1G>A突变（GJB2）与雅库特人中IVS1+1G>A携带者的年龄相关性听力减退（ARHI）有关。
