New prognostic markers of hearing impairment in children: gene-gene interaction and approximation models

L. P. Sydorchuk, O. M. Iftoda



Objective: to evaluate the gene-gene interaction, assess the risks and develop some approximation models of hearing loss / deafness occurrence in children, depending on the genes polymorphism gab junction B2 (GJB2, rs80338939), and interleukin-4 (IL-4, rs 2243250) and other risk factors.

Materials and methods: Study included 102 children with hearing impairment: 68 with sensorineural (SNHL) and 34 with conductive hearing loss (CHL), among them 36 (35.29%) girls and 66 (64.71%) boys. The patients' age vary from 8 to 18 yo (on the average 13.90±3.11 yo). Diagnosis set by otorhinolaryngology (ENT) methods: ENT examination, computer audiometry, impedancemetry, tympanometry. The control group included 60 practically healthy children: 22 girls (36.67%), 38 boys (63.33%). Polymorphism of GJB2 (rs80338939) and IL-4 (rs 2243250) genes was studied by polymerase chain reaction method. Risk assessed by Relative Risk, Odds Ratio and 95% Confidential intervals.

Results. The combination of 35delG / TT, as well as Non-Del / TT and 35delG/ TC genotypes in the genome is associated with a high risk of hearing loss in general children population (from 0.932 to 1.432; OR=19.5; p=0.003), as well as the appearance SNHL (from 0.765 to 1.765), stronger than the combination of unfavorable homozygotes TT / 35DelG - 1.765. The combination of homozygotes for the wild allele of both genes (especially CC / Non-Del) is associated with a low risk of deafness: hearing loss in general -1,068, for SNHL -0,908, for CHL -0,750 (p<0,01), for CC / 35delG combination, or TC / Non-Del: in general -0.068 -, and for SNHL -0.235 and -0.11 respectively, (p>0.05).

Infectious diseases in anamnesis (meningitis, measles, mumps, or rubella) increases the likelihood of CHL by 9.41 times (OR=12.0; p=0.007). Concomitant chronic non-obstructive and obstructive upper and lower respiratory tract diseases increase the risk of both SNHL and CHL in children regardless of age: for SNHL 3.75-7.81 times (OR=6.50-10.9; p≤0.028-0.01), for CHL – 4.29-8.75 times (OR=6.19-12.9; p≤0.03-0.009). The revealed dependence of the indicators is best described by the logit-regression approximating models with high multiple correlation coefficient (R2=0.9761); low standard error of the model estimation (ε=0.1114); connection criterion F=124.2; degrees of freedom df=7.43 (p<0.001).

Conclusions: Genes polymorphism's GJB2 (rs80338939) and IL-4 (rs 2243250) and their interactions are new prognostic markers of hearing impairment in children. Approximating models describe the likelihood of SNHL and CHL in observed population.


sensorineural; conductive hearing loss; deafness; genes GJB2; IL-4; markers; approximation; models; prognosis; children

Full Text:



Deafness and hearing loss. WHO. Health Topic. Updated 2020. Accessed 23 July, 2020.

Basic ear and hearing care resource. WHO. Published 25 February, 2020. Accessed 23 July, 2020.

Hearing, Ear Infections, and Deafness. National Institute on Deafness and Other Communication Disorders (NIDCD). U.S. Department of Health & Human Services. National Institutes of Health. Updated 2020. Accessed 23 July, 2020.

Capron L. What's in a risk factor? "He who strikes the ball". Diabetes & Metabolism. 2003;29(1):6-13.

Smith RJH, Hildebrand MS, Van Camp G. Deafness and Hereditary Hearing Loss Overview. GeneReviews® [Internet]. Updated July 27, 2017. Accessed 23 July, 2020.

Highlighting priorities for ear and hearing care - World Report on Hearing. WHO. Activities. Updated 2020. Accessed 23 July, 2020.

Iftoda OM. Role of risk factors in the formation of sensorineural and conductive deafness, hearing loss in children. Bukovinian Medical Herald. 2015;19(3(75)):53-57. (In Ukrainian)

Iftoda OM, Mamalyga IS, Sydorchuk LP. Comorbidities as risk factors of hearing loss and deafness formation in children. Clinical & Experimental Pathology. 2015;XIV(2(52)):285-290. (In Ukrainian)

Iftoda OM, Mamalyga IS, Sydorchuk LP. Mechanisms and patterns of immune system changes in children with deafness and hearing loss. Bulletin of Scientific Research. 2015;4(81):77-80. (In Ukrainian)

Iftoda OM, Sydorchuk LP. Cytokine mechanisms of immunological disorders in children of Bukovina with deafness depending on polymorphisms of connexin-26 CJB2 (rs80338939) and interleukin-4 (rs2243250) genes. Journal of Clinical and Experimental Medical Research. 2016;4(1):27-35. (In Ukrainian)

Sydorchuk L, Iftoda O, Sydorchuk A, Kushnir O, Sydorchuk R. Cytokines' cascade changes in children with hearing loss depending on gapjunction protein beta 2 (C.35delG) and interleukin 4 (C-590T) genes polymorphism. The Pharma Innovation Journal. 2016;5(2):22-27.

Iftoda ОM, Sydorchuk LP, Kushnir ОV, Repchuk YuV. Immunological Reactivity and Nonspecific Resistance in Children with Hearing Loss Depending on Genes' Polymorphic Variants CJB2 (C.35DelG) and IL-4 (C-590T). European Journal of Medicine. Series B. 2016;5(1):4-11.

Sydorchuk LP, Iftoda ОM, Kushnir ОV. Genes polymorphism of Connexin 26 (GJB2) and Interleukin 4 (C-590T) in children of Bukovina with hearing loss. Likars'ka sprava / Ministerstvo okhorony zdorov'ia Ukraïny. 2016;5-6:25-30. (In Ukrainian)

Rabionet R, Gasparini P, Estivill X. Molecular genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins. Hum Mutat. 2000;16(3):190-202.

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Journal of Education, Health and Sport formerly Journal of Health Sciences

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