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CYTOKINE MECHANISMS OF IMMUNOLOGICAL DISORDERS IN CHILDREN OF BUKOVINA WITH DEAFNESS DEPENDING ON POLYMORPHISMS OF CONNEXIN-26 CJB2 (RS80338939) AND INTERLEUKIN-4 (RS2243250) GENES

Аuthors: O. M. Iftoda, L. P. Sydorchuk

Pages: 27–35

Abstract

Introduction. 360 million people worldwide have disabling hearing loss. Hearing loss may result from genetic causes, complications at birth, certain infectious diseases, chronic ear infections, the use of particular drugs, exposure to excessive noise and ageing. About 100 genes in the human body responsible for the hearing organ formation and function. Over 50 % of autosomal recessive forms of hearing loss associated with mutations in the gene connexin-26 CJB2 (gap junction protein, beta 2), localized in 13q11-q12. However, at present there are no recommendations on the use of molecular genetic tests in the early diagnosis of deafness. Debatable issues nowadays are the genetic factors impact on the type and degree of hearing loss, immune response changes, etc.

Purpose. To evaluate some immunological mechanisms of sensorineural (SNHL) and conductive hearing loss (CHL) development in children after pro- and antiinflammatory cytokine levels depending on genes polymorphism of connexin-26 (CJB2, c.35delG) (rs80338939) and interleukin-4 (IL-4, C-590T) (rs 2243250).

Materials and Methods. 102 screened children (8-18 years): 68 (66.7 %) children with SNHL, 34 (33.3 %) with CHL. The control group consisted of 30 healthy individuals. Levels of cytokines: tumor necrosis factor alpha (TNF-α), IL-1β, IL-4, IL-10 and IL-13 in plasma were determined by ELISA. Study of gene polymorphisms of IL-4 (C-590T) and CJB2 (c.35delG) performed by polymerase chain reaction. Statistical processing was performed with Statistica® 7.0 software. The differences were considered significant at p < 0.05.

Results. SNHL and CHL course in children is associated with a decreased concentration of IL-1β in the peripheral venous blood plasma by 36.06 % and 29.53 %, increased of IL-4 1.69 (р < 0.05) and 2.68 times (р = 0.013) and different changes of TNFα content (increases in CHL children, reduces in SNHL cases), IL-10 and IL-13 (contrary, it increases in SNHL children and decreases in CHL subjects).

The imbalance of the immune response in children with SNHL characterized by inhibition of cellular immunity and activation of humoral answer caused by low TNF-α and IL-1β content in CT-, TT-genotype carriers of IL-4 gene – 2.42 (p = 0.032) and 2.02 times (p = 0.042) with the antiinflammatory IL-4 and IL-10 cytokines hyperproduction 4.4-16.45 times (p ≤ 0.005). CHL TT genotype carriers of IL-4 gene followed by increased TNF-α 1.69 times (p = 0.033) and IL-4 35.71 times (p < 0.001), low levels of IL-10 3.11-4.44 times (p ≤ 0.01) and IL-13 – 1.66-2.72 times (p ≤ 0.026) respectively. But, in the mutational 35delG-carriers of the CJB2 gene the CHL course is associated with reduced TNFα, IL-1β, IL-4, IL-10 production with preserved IL-13 synthesis. It proved the cellular and humoral immune response reduced activity and an increased risk of allergic reactions.

Conclusion: SNHL in the T-allele carriers' children characterized by decreased activity of antiinfectious nonspecific immune defense factors. CHL course associated with cell immune response activation (mainly) and humoral part (less) as well.

 Keywords: sensorineural, conductive deafness, children, cytokines, genes CJB2, IL-4.

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