mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-ROT-2271mimmun-2435Research ArticleМАТЕРИАЛЫ ФОРУМА "ДНИ ИММУНОЛОГИИ В СПБ" 2021РОЛЬ ПОЛИМОРФИЗМА ГЕНОВ TLR2, TLR4 В ФОРМИРОВАНИИ МИКРОСОСУДИСТЫХ ОСЛОЖНЕНИЙ У ПОДРОСТКОВ С САХАРНЫМ ДИАБЕТОМ 1-ГО ТИПАROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUSВоропайA. A.VoropaiA. A.

врач детский эндокринолог детского эндокринологического отделения, 

344012, г. Ростов-на-Дону, ул. Мечникова, 43

Pediatric Endocrinologist of Pediatric Endocrinology Department, 

344012, Rostov-on-Don, Mechnikov str., 43

goli-an@yandex.ruЛевковичM. A.LevkovichM. A.

д.м.н., доцент, ведущий научный сотрудник отдела медико-биологических проблем в акушерстве, гинекологии и педиатрии,

344012, г. Ростов-на-Дону, ул. Мечникова, 43

PhD, MD (Medicine), Associate Professor, Leading Research Associate, Department of Biomedical Problems in Obstetrics, Gynecology and Pediatrics,

344012, Rostov-on-Don, Mechnikov str., 43

ГалкинаГ. А.GalkinaG. A.

д.м.н., главный внештатный детский эндокринолог ЮФО и МЗ РО, заведующая детским эндокринологическим отделением;

профессор кафедры «Эндокринологии с курсом детской эндокринологии» ФПК и ППС,

344012, г. Ростов-на-Дону, ул. Мечникова, 43

PhD, MD (Medicine), Сhief Outside Pediatric Endocrinologist of the Southern Federal District and Ministry of Health of the Rostov Region, Head, Pediatric Endocrinology Department;

Professor, Department of Endocrinology with the Course of Pediatric Endocrinology,

344012, Rostov-on-Don, Mechnikov str., 43

КомковаМ. В.KomkovaM. V.

к.м.н., врач детский эндокринолог детского эндокринологического отделения,

344012, г. Ростов-на-Дону, ул. Мечникова, 43

PhD (Medicine), Pediatric Endocrinologist of Pediatric Endocrinology Department,

344012, Rostov-on-Don, Mechnikov str., 43

МорозоваМ. В.MorozovaM. V.

к.м.н., врач детский эндокринолог детского эндокринологического отделения,

344012, г. Ростов-на-Дону, ул. Мечникова, 43

PhD (Medicine), Pediatric Endocrinologist of Pediatric Endocrinology Department, 

344012, Rostov-on-Don, Mechnikov str., 43

Научно-исследовательский институт акушерства и педиатрии ФГБОУ ВО «Ростовский государственный медицинский университет» Министерства здравоохранения РФРоссияResearch Institute of Obstetrics and Pediatrics, Rostov State Medical UniversityRussian Federation202119102021234895902Copyright © Воропай A.A., Левкович M.A., Галкина Г.А., Комкова М.В., Морозова М.В., 20212021Воропай A.A., Левкович M.A., Галкина Г.А., Комкова М.В., Морозова М.В.Voropai A.A., Levkovich M.A., Galkina G.A., Komkova M.V., Morozova M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2435

Отсроченные осложнения сахарного диабета 1-го типа (СД1) у детей и подростков являются важной проблемой современной медицины. В последние годы активно обсуждается роль иммунных механизмов, в частности хронического воспаления в развитии как СД1, так и его микрососудистых осложнений. Активация Toll-like рецептора 2 (TLR2) и Toll-like рецептора 4 (TLR4) приводит к индукции синтеза провоспалительных цитокинов, хемокинов, молекул адгезии, участвующих в формировании диабетических микрососудистых осложнений. При этом наличие генетического полиморифизм TLR2 и TLR4 изменяет иммунное реагирование в ответ на их стимуляцию эндогенными лигандами, что может повышать риск возникновения диабетических микроангиопатий. Цель исследования – изучить распределение частот генотипов и аллелей генов TLR2 и TLR4 и определить содержание TNFα, IL-1, VCAM-1, фракталкин, эндотелин-1 у подростков с СД1 и микрососудистыми осложнениями. Обследовано 139 подростков с СД1 от 14 до 18 лет и 56 здоровых подростков. Пациенты с СД1 распределены на две группы: I группа – пациенты с декомпенсацией СД1, (HbA1C > 9,0%), (n = 64); II группа – пациенты с удовлетворительным гликемическим контролем СД1 (HbA1C ≤ 9,0%), (n = 75). В зависимости от наличия осложнений выделены 4 подгруппы: Iа (n = 49), IIа (n = 38) – подростки с микрососудистыми нарушениями: Iб (n = 15), IIб (n = 37) – с неосложненным течением заболевания. Определение аллельных вариантов генов TLR проводили с использованием тест-систем ГосНИИ генетика (Москва). Определение содержания цитокинов в сыворотке крови осуществлялось методом твердофазного иммуноферментного анализа BIOSCIENCE. Обработка данных проводилась с использованием пакетов прикладных программ Statistica 6.0. При изучении распределения полиморфизмов TLR2 (Arg753Gln) и TLR4 (Thr399Ile) не было выявлено достоверных различий между исследуемыми подгруппами и контролем. Отмечено, что вариант Asp299Gly в Iа и IIа подгруппах (с осложненным течением) встречался достоверно реже, чем в Iб, IIб подгруппах и контролем. Установлено, что наличие аллеля Gly в гене TLR4 влияет на уровень экспрессии TNFα и VCAM-1 в сыворотке крови и может считаться протективным по развитию микрососудистых осложнений. 

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. 

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The authors declare that there are no conflicts of interest present.