ROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

Long-term complications of type 1 diabetes mellitus (T1DM) in children and adolescents are an important problem in modern medicine. Recently, the role of immune mechanisms, in particular, chronic inflammation, in the development of both T1DM and its microvascular complications has been actively disc...

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Autores principales:	A. A. Voropai, M. A. Levkovich, G. A. Galkina, M. V. Komkova, M. V. Morozova
Formato:	article
Lenguaje:	RU
Publicado:	SPb RAACI 2021
Materias:	type 1 diabetes mellitus adolescents microvascular complications tlr receptors gene polymorphism cytokines Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/37accd6e01e24f43afa791c4b544bb49
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spelling	oai:doaj.org-article:37accd6e01e24f43afa791c4b544bb492021-11-18T08:03:51ZROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS1563-06252313-741X10.15789/1563-0625-ROT-2271https://doaj.org/article/37accd6e01e24f43afa791c4b544bb492021-10-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/2435https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XLong-term complications of type 1 diabetes mellitus (T1DM) in children and adolescents are an important problem in modern medicine. Recently, the role of immune mechanisms, in particular, chronic inflammation, in the development of both T1DM and its microvascular complications has been actively discussed. Activation of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) leads to hyperproduction of proinflammatory cytokines, chemokines, adhesion molecules involved in the formation of diabetic microvascular complications. At the same time, TLR2 and TLR4 gene polymorphism alters the immune susceptibility to the endogenous ligands, which may increase the risk of diabetic microangiopathies. The aim of this study is to evaluate the frequency of genotypes and alleles of TLR2 and TLR4 genes distribution and to determine the content of TNFα, IL-1, VCAM-1, fractalkine, endothelin-1 in adolescents with T1DM with microvascular complications. We examined 139 adolescents with T1DM from 14 to 18 years old and 56 healthy teenagers. Patients with T1DM were divided into two groups: Group I – patients with poor glycemic control (HbA1C > 9.0%), (n = 64); Group II – patients with satisfactory glycemic control of T1DM (HbA1C ≤ 9.0%), (n = 75), including adolescents with optimal (HbA1C < 7.5%) and suboptimal glycemic control (7.5% ≤ HbA1C ≤ 9.0%) (ISPAD clinical practice consensus guidelines 2014). According to the presence of microvascular complications, the groups were subdivided into subgroups: Iа (n = 49), IIа (n = 38) – adolescents with verified microvascular disorders: diabetic retinopathy, nephropathy and neuropathy; Ib (n = 15), IIb (n = 37) – without microvascular complications. Allelic variants of TLR genes were determined using test systems GosNII genetics (Moscow). The content of cytokines in blood serum was carried out by the method of enzyme-linked immunosorbent assay “BIOSCIENCE”. Data were analyzed using software packages Statistica version 6.0. The assessment of TLR2 (Arg753Gln) and TLR4 (Thr399Ile) polymorphism distribution did not reveal significant differences between the observed subgroups and the control. In Ia and IIa subgroups (with complications) Asp299Gly variant was noted to be significantly less common when compared to subgroups Ib, IIb and controls. The presence of Gly allele in TLR4 gene was found to disrupt the expression of TNFα and VCAM-1 and can be considered protective for the development of microvascular complications.A. A. VoropaiM. A. LevkovichG. A. GalkinaM. V. KomkovaM. V. MorozovaSPb RAACIarticletype 1 diabetes mellitusadolescentsmicrovascular complicationstlr receptors gene polymorphismcytokinesImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 23, Iss 4, Pp 895-902 (2021)
institution	DOAJ
collection	DOAJ
language	RU
topic	type 1 diabetes mellitus adolescents microvascular complications tlr receptors gene polymorphism cytokines Immunologic diseases. Allergy RC581-607
spellingShingle	type 1 diabetes mellitus adolescents microvascular complications tlr receptors gene polymorphism cytokines Immunologic diseases. Allergy RC581-607 A. A. Voropai M. A. Levkovich G. A. Galkina M. V. Komkova M. V. Morozova ROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS
description	Long-term complications of type 1 diabetes mellitus (T1DM) in children and adolescents are an important problem in modern medicine. Recently, the role of immune mechanisms, in particular, chronic inflammation, in the development of both T1DM and its microvascular complications has been actively discussed. Activation of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) leads to hyperproduction of proinflammatory cytokines, chemokines, adhesion molecules involved in the formation of diabetic microvascular complications. At the same time, TLR2 and TLR4 gene polymorphism alters the immune susceptibility to the endogenous ligands, which may increase the risk of diabetic microangiopathies. The aim of this study is to evaluate the frequency of genotypes and alleles of TLR2 and TLR4 genes distribution and to determine the content of TNFα, IL-1, VCAM-1, fractalkine, endothelin-1 in adolescents with T1DM with microvascular complications. We examined 139 adolescents with T1DM from 14 to 18 years old and 56 healthy teenagers. Patients with T1DM were divided into two groups: Group I – patients with poor glycemic control (HbA1C > 9.0%), (n = 64); Group II – patients with satisfactory glycemic control of T1DM (HbA1C ≤ 9.0%), (n = 75), including adolescents with optimal (HbA1C < 7.5%) and suboptimal glycemic control (7.5% ≤ HbA1C ≤ 9.0%) (ISPAD clinical practice consensus guidelines 2014). According to the presence of microvascular complications, the groups were subdivided into subgroups: Iа (n = 49), IIа (n = 38) – adolescents with verified microvascular disorders: diabetic retinopathy, nephropathy and neuropathy; Ib (n = 15), IIb (n = 37) – without microvascular complications. Allelic variants of TLR genes were determined using test systems GosNII genetics (Moscow). The content of cytokines in blood serum was carried out by the method of enzyme-linked immunosorbent assay “BIOSCIENCE”. Data were analyzed using software packages Statistica version 6.0. The assessment of TLR2 (Arg753Gln) and TLR4 (Thr399Ile) polymorphism distribution did not reveal significant differences between the observed subgroups and the control. In Ia and IIa subgroups (with complications) Asp299Gly variant was noted to be significantly less common when compared to subgroups Ib, IIb and controls. The presence of Gly allele in TLR4 gene was found to disrupt the expression of TNFα and VCAM-1 and can be considered protective for the development of microvascular complications.
format	article
author	A. A. Voropai M. A. Levkovich G. A. Galkina M. V. Komkova M. V. Morozova
author_facet	A. A. Voropai M. A. Levkovich G. A. Galkina M. V. Komkova M. V. Morozova
author_sort	A. A. Voropai
title	ROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS
title_short	ROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS
title_full	ROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS
title_fullStr	ROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS
title_full_unstemmed	ROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS
title_sort	role of tlr2, tlr4 gene polymorphism in developing microvascular complications in adolescents with type 1 diabetes mellitus
publisher	SPb RAACI
publishDate	2021
url	https://doaj.org/article/37accd6e01e24f43afa791c4b544bb49
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ROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

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