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

L. P. Sydorchuk, O. M. Iftoda

DOI: http://dx.doi.org/10.12775/JEHS.2020.10.06.039

Abstract


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.


Keywords


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

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References


Deafness and hearing loss. WHO. Health Topic. https://www.who.int/health-topics/hearing-loss#tab=tab_1. Updated 2020. Accessed 23 July, 2020.

Basic ear and hearing care resource. WHO. https://www.who.int/publications/i/item/basic-ear-and-hearing-care-resource. 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. https://www.nidcd.nih.gov/health/hearing-ear-infections-deafness. 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]. http://www.ncbi.nlm.nih.gov/books/NBK1434. Updated July 27, 2017. Accessed 23 July, 2020.

Highlighting priorities for ear and hearing care - World Report on Hearing. WHO. Activities. https://www.who.int/activities/highlighting-priorities-for-ear-and-hearing-care. 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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