ABSTRACT
The objective of the present work was to study the role of GST genes in pathogenesis of various neurodegenerative conditions with special reference to sensorineural impairment of hearing. The DNA samples obtained from 200 subjects were available for the investigation; 109 of them were the patients hospitalized in the otorhinolaryngologcal clinic of S.M. Kirov Military Medical Academy for the treatment of uni- or bilateral impairment of hearing. The polymerase chain reaction with subsequent specific restriction endonuclease analysis was used to study genetic mutations. The analysis was focused on the 35delG mutation in the GJB2 gene (DFNB1). In addition, the MTRNR1 (12S rRNA) and MTTS1 (serine tRNA) genes in the patients with acquired sensorineural impairment of hearing were subjected to analysis. Polymorphism of the second detoxication phase gene (GSTM1) was investigated. It was shown that mitochondrial genes MTRNR1 and MTTS1 contribute to the development of acquired sensorineural impairment of hearing. The frequency of heterozygous 35delG mutations of the GJB2 (DFNB1) gene among the subjects with impaired hearing does not significantly differ from its prevalence in the general population. The allelic mutation of the GSTM1 gene is believed to be a predisposing factor for the development of sensorineural impairment of hearing under the action of intoxication and/or infections.
Subject(s)
Connexins/genetics , Glutathione Transferase/genetics , Hearing Loss, Sensorineural , Point Mutation , Adult , Connexin 26 , Female , Gene-Environment Interaction , Genetic Predisposition to Disease/epidemiology , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/epidemiology , Hearing Loss, Sensorineural/genetics , Hearing Tests/methods , Humans , Male , Polymorphism, Genetic , PrevalenceABSTRACT
Mitochondrial DNA (mtDNA) mutations play an important role in etiology of hereditary hearing loss. In various regions of the world, patients suffer from nonsyndromic sensorineural hearing loss initiated by aminoglycoside antibiotics. Mutations that had been shown as pathogenetically important for hearing function disturbance were identified in mitochondrial 12S rRNA and tRNA(Ser(UCN)) genes while pathogenic role of several DNA sequences requires additional studies. This work presents the results of studying the spectrum of mutations and polymorphic variations in mtDNA genes 12S rRNA and tRNA(Ser(UGN)) in 410 patients with nonsyndromal sensoneural hearing impairment/loss from the Volga Ural region, St Petersburg, Yakutia, and Altai and in 520 individuals with normal hearing, which represent several ethnic groups (Russians, Tatars, Bashkirs, Yakuts, Altaians) residing in the Russian Federation. Pathogenetically significant mutation A1555G (12S rRNA) was found in two families (from Yakutia and St Peresburg) with hearing loss, probably caused by treatment with aminoglucosides, and in the population sample of Yakuts with a frequency of 0.83%. Further research is needed to confirm the role in hearing impairment of mutations 961insC, 961insC(n), 961delTinsC(n), T961G, T1095C (12S rRNA) and G7444A, A7445C (tRNA(Ser(UGN revealed in the patients. In addition, in the patients and the population groups, polymorphic mt DNA variants were detected, which are characteristic also of other Eurasian populations both in spectrum and frequency.
