Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1819010.15789/2220-7619-PIC-18190ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИUnknownPRO-INFLAMMATORY CYTOKINE POLYMORPHISMS IN PATIENTS WITH VARYING COVID-19 SEVERITY FROM THE WEST SIBERIAN REGION OF RUSSIAПолиморфизм провоспалительных цитокинов у пациентов Западно-Сибирского региона России с разной тяжестью течения COVID-19https://orcid.org/0000-0001-5898-950XShevchenkoAlla V.ШевченкоАлла Владимировна
Russian Federation

DSc (Biology), Leading Researcher, Laboratory of Clinical Immunogenetics

д.б.н., ведущий научный сотрудник лаборатории клиничеcкой иммуногенетики

shalla64@mail.ruhttps://orcid.org/0000-0001-7385-6270KonenkovVladimir IosiphovichКоненковВладимир Иосифович
Russian Federation

MD, PhD, Dr. Med. Sci., Professor, Academician of Russian Academy of Science, Head of the Laboratory of Clinical Immunogenetics RICEL- Branch of IC&G SB RAS,

доктор медицинских наук, профессор, академик РАН, руководитель лаборатории клинической иммуногенетики НИИКЭЛ - филиал ИЦиГ СО РАН, Научный руководитель НИИКЭЛ - филиал ИЦиГ СО РАН

vikonenkov@gmail.comhttps://orcid.org/0009-0002-4513-9666DolmatovaAnastasia AlekseevnaДолматоваАнастасия Алексеевна
Russian Federation

Junior Researcher Laboratory of Clinical Immunogenetics

младший научный сотрудник лаборатории клинической иммуногенетики НИИ клинической и экспериментальной лимфологии

a.dolmatova@g.nsu.ruhttps://orcid.org/0000-0002-0423-5021KarasevaAlexandra AleksandrovnaКарасеваАлександра Александровна
Russian Federation

Junior Researcher of the Laboratory of Genetic and Environmental Determinants of the Human Life Cycle IIPM

младший научный сотрудник лаборатории генетических и средовых детерминант жизненного цикла человека

Sas96@bk.ruhttps://orcid.org/0000-0001-7875-1566AfanasevaAlena DmitrievnaАфанасьеваАлёна Дмитриевна
Russian Federation

MD, PhD, head Laboratory of Genetic and Environmental Determinants of the Human Life Cycle IIPM

кандидат медицинских наук, руководитель лаборатории генетических и средовых детерминант жизненного цикла человека НИИТПМ

alena.dmytryevna@yandex.ruhttps://orcid.org/0000-0003-1348-0253LogvinenkoIrina IvanovnaЛогвиненкоИрина Ивановна
Russian Federation

Dr. Med. Sci., Professor, Chief Researcher of the Laboratory of Preventive Medicine IIPM

доктор медицинских наук, профессор, главный научный сотрудник лаборатории профилактической медицины

111157@mail.ruBranch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation«Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, Российская Федерация290920260304202628072026Copyright ©; , Shevchenko A.V., Konenkov V.I., Dolmatova A.A., Karaseva A.A., Afanaseva A.D., Logvinenko I.I.Copyright ©; , Шевченко А.В., Коненков В.И., Долматова А.А., Карасева А.А., Афанасьева А.Д., Логвиненко И.И.Shevchenko A.V., Konenkov V.I., Dolmatova A.A., Karaseva A.A., Afanaseva A.D., Logvinenko I.I.Шевченко А.В., Коненков В.И., Долматова А.А., Карасева А.А., Афанасьева А.Д., Логвиненко И.И.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/18190

In patients with SARS‑CoV‑2, increased level and disturbed pro‑inflammatory cytokine profile correlating with COVID-19 severity and mortality is observed. TNF-α, IL-1β, IL-6 are of the key effector molecules. Higher rates of hospitalization and mortality are noted among elderly and patients with chronic diseases. Various risk factors, such as genetic predisposition, can influence the disease course. The aim: to analyze a relationship between the functional polymorphisms of TNFa (rs1800630, rs1800629, rs361525), IL1b (rs1143627), IL6 (rs1800795) genes and the severity of COVID-19, taking into account the concomitant factors of the aggravating infectious process. There were enrolled 260 COVID-19 two months after recovery stratified into 3 subgroups according to the disease severity: mild, moderate, severe infection. TNFa (rs1800630, rs1800629, rs361525), IL1b (rs1143627), IL6 (rs1800795) were genotyped using TagMan. Statistical processing was performed using the IBM SPSS Statistics. The multivariate regression analysis was performed. The dependent variable was the severity of COVID, the independent variables included patient genotype, gender, and age. No inter-group differences were found in the frequencies of the TNF(-238, -308, -863) and IL-6-174 genotypes while assessing severity level of the disease. IL1-31 CC genotype was found to be at significantly higher level in patients with severe and moderate course of the infectious process vs mild form. Carriers of four complex genotypes were more likely to experience a severe form of the disease. In the group with normal BMI, IL1‑31 CC is an increase. The IL6-174 GG is more common in patients who experienced a milder course of the disease in this subgroup. A multifactorial regression analysis, taking into account patient gender and age, showed that genetic component independently contributed to the severity of COVID‑19. Thus, conducting this type of research in Russia with its general population being largely composed of individuals of Caucasian and Mongoloid descent as well as their descendants with varying degrees of mixed ancestry is extremely relevant to further explore potential clinical application of final results upon increasing comorbidity.

При SARS-CoV-2 инфицировании у пациентов отмечается повышение уровня и дисбаланс провоспалительных цитокинов, что коррелирует с тяжестью заболевания и смертностью. В качестве одной из ключевых эффекторных молекул рассматривается TNF-α. Повышенный уровень IL-1β и IL-6 также коррелируют с тяжелыми симптомами у пациентов. При этом более высокие показатели госпитализации и смертности наблюдаются среди возрастных пациентов и пациентов с наличием хронических заболеваний. Это свидетельствует в пользу того, что иные факторы риска, например, генетическая предрасположенность, могут влиять на протекание заболевания. Цель: проанализировать связь между функциональным полиморфизмом генов TNFα (rs1800630, rs1800629, rs361525), IL1β (rs1143627), IL6 (rs1800795) и тяжестью течения COVID-19, учитывая сопутствующие факторы отягощения инфекционного процесса. В исследование включено 260 пациентов, переболевших COVID-19 через два месяцев после реконвалесценции. Учитывались пол, возраст, ИМТ, наличие хронических заболеваний. Выделялись 3 субгруппы по тяжести COVID-19:с легким, со среднетяжёлым, с тяжелым течением инфекции. Генотипирование TNFα (rs1800630, rs1800629, rs361525), IL1β (rs1143627), IL6 (rs1800795) осуществляли методом TagMan зондов. Статистическая обработка проводилась с использованием статистического пакета IBM SPSS Statistics. Дополнительно проводился многомерный регрессионный анализ с использованием логистической регрессии. Зависимой переменной являлась тяжесть течения COVID, независимые переменные - генотип, пол и возраст пациентов. Не выявлено различий частот генотипов TNF(-238, -308, -863) и IL-6-174 между группами с разной степенью тяжести протекания заболевания - тяжелой - средней - легкой. Частота генотипа IL1-31 СС значимо выше у пациентов с тяжелым и средне - тяжелым протеканием инфекционного процесса относительно пациентов, перенесших заболевание в легкой форме. Выявлено четыре комплекса генотипов, носители которых чаще переносили заболевание в тяжелой форме. В группе с нормальным ИМТ наблюдается повышение минорного генотипа гена IL1-31 СС, причем отношения шансов развития тяжелой + среднетяжелой формы протекания заболевания у пациентов с нормальным ИМТ выше, чем в общей группе больных. Генотип IL6-174GG достоверно выше у пациентов, перенесших заболевание в более легкой форме в этой субгруппе. Проведенный многофакторный регрессионный анализ с учетом таких переменных, как пол и возраст пациентов показал независимый вклад генетической составляющей в степень тяжести протекания COVID-19. Таким образом, в России с ее значительным представительством европеоидного и монголоидного населения, а также их метизированных в различной степени потомков, проведение такого рода исследований является чрезвычайно актуальным в перспективе клинического применения их результатов в условиях нарастающей коморбидности.

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