Genetic regulation of cytokine inflammation in oncohematological diseases

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Abstract

Objective. To analyze the correlations of the polymorphous variants of the genes – the modifiers of immune response (IL1-β/+3953, IL1RN*VNTR, TNFA*G-308A) with the development of oncohematological diseases (OHD) and the production of pro-and anti-inflammatory cytokines (IL-1β, IL-1Ra, TNF-α, INF-γ, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18).

Materials and methods. The examination included 100 children (57 (57 %) boys и 43 (43 %) girls, with the mean age 7.50 (2.5–12.60 years) suffering from malignant blood diseases. The cytokine content (IL-1β, IL-4, IL-6, IL-8, IL-18, IL-1Ra и IL-10) was determined using IFA, the genetic typing of the genetic variants of the genes of cytokines IL1-β/+3953, IL1RN*VNTR, TNFA*G-308A – PCR and RFLP methods.

Results. In case of lethal outcome, 14% of cases, the TNF-α IL-6, IL-8, IL-18 INF-γ and IL-10 levels were reliably higher, compared with the survived patients. Renal function disorder detected among 13% of children was accompanied by an increase in IL-1β, IL-6, IL-8, IL-18, IL-1Ra and INF-γ compared to the patients without nephropathy and the control group (p<0.05). Eighteen OHD children with high concentration of IL-1β, IL-1Ra, IL-6, IL-8, IL-18 and INF-γ had fractures (р<0,05). Against the background of OHD, the carriage of the genotype А2А2 of the polymorphic variant VNTR IL1RN gene was observed 13 times more often, the carriage of the allele A2 – 2.16 times more often. The carriers of the genotype A2A2 of the genetic variant VNTR IL1RN gene had an increased risk of nephropathy by 20.89 times, the carriers of the allele A2 – 3.05 times more often. Children with OHD complicated by bacterial infection by 10.77 times more often had the genotype A2A2 and by 2.45 times more often – the allele A2 of the genetic variant VNTR IL1RN gene.

Conclusions. The carriers of the minor genotype A2A2 of the gene IL1RN*VNTR had a reliably higher production of the antiinflammatory IL-1β, IL-6, IL-8, IL-18 и IL-1Ra. The carriers of the genotype GA of the gene TNFA*G-308A had a significantly higher values of IL-1β, IL-18, IL-6, IL-8, TNF-α.

About the authors

E. V. Loshkova

Scientific Research Clinical Institute of Childhood of the Ministry of Health of the Moscow Region

Author for correspondence.
Email: loshkova@rambler.ru
ORCID iD: 0000-0002-3043-8674

Candidate of Medical Sciences, senior researcher of Department of Congenital and Metabolic Diseases

Russian Federation, Moscow

Yu. B. Ponomarenko

Children's Regional Clinical Hospital

Email: loshkova@rambler.ru
ORCID iD: 0000-0002-9326-4085

pediatrician

Russian Federation, Krasnodar

E. I. Kondratieva

Scientific Research Clinical Institute of Childhood of the Ministry of Health of the Moscow Region

Email: loshkova@rambler.ru

MD, PhD, Professor, Head of the Scientific and Clinical Department of Cystic Fibrosis

Russian Federation, Moscow

V. V. Lebedev

Children's Regional Clinical Hospital

Email: loshkova@rambler.ru

Head of Unit of Oncology and Hematology with Chemotherapy

Russian Federation, Krasnodar

E. I. Kleschenko

Children's Regional Clinical Hospital; Kuban State Medical University

Email: loshkova@rambler.ru
ORCID iD: 0000-0003-0322-4715

Chief Physician, Head of Department of Pediatrics with Course of Neonatology

Russian Federation, Krasnodar; Krasnodar

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Copyright (c) 2022 Loshkova E.V., Ponomarenko Y.B., Kondratieva E.I., Lebedev V.V., Kleschenko E.I.

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