rmtОбщая реаниматологияGeneral Reanimatology1813-97792411-7110FSBI "SRIGR" RAMS10.15360/1813-9779-2021-5-35-51rmt-2134Research ArticleКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯCLINICAL STUDIESВклад полиморфизма промоторной области гена AGTR 1 в течение и исход сепсиса у пациентов с различной коморбидностьюContribution of AGTR 1 Promoter Region Polymorphism to the Progression and Outcome of Sepsis in Patients with Various ComorbiditiesЧумаченкоА. Г.ChumachenkoA. G.

107031, Москва, ул. Петровка, д. 25, стр. 2.

Anastasia G. Chumachenko.25 Petrovka Str., Bldg. 2, 107031 Moscow.

ГригорьевЕ. К.GrigorievE. K.

107031, Москва, ул. Петровка, д. 25, стр. 2.

Evgeniy K. Grigoriev.25 Petrovka Str., Bldg. 2, 107031 Moscow.

ПисаревВ. М.PisarevV. M.

Писарев Владимир Митрофанович.107031, Москва, ул. Петровка, д. 25, стр. 2.

Vladimir M. Pisarev.25 Petrovka Str., Bldg. 2, 107031 Moscow.

vpisarev@gmail.comНИИ общей реаниматологии им. В.А. Неговского ФНКЦ РРРоссияV.A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and RehabilitologyRussian Federation2021231020211753551Copyright © Чумаченко А.Г., Григорьев Е.К., Писарев В.М., 20212021Чумаченко А.Г., Григорьев Е.К., Писарев В.М.Chumachenko A.G., Grigoriev E.K., Pisarev V.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.reanimatology.com/rmt/article/view/2134

Значительный вклад в течение сепсиса и особенно септического шока вносят дисрегуляция артериального давления и развитие циркуляторной недостаточности. Одним из генов, влияющих на состояние эндотелия сосудистой стенки и тонуса артериол, является ген рецептора 1 к ангиотензину II (AGTR1). Однонуклеотидный полиморфизм AGTR1 rs275651 ассоциирован с развитием стенокардии, отека легких в условиях высокогорья, гипертензии. Значение полиморфизма AGTR1 rs275651 при сепсисе, в том числе — в группах пациентов в сочетании с выраженной коморбидностью, ранее исследовано не было.Цель исследования — определение вклада функционального полиморфизма AGTR1 в исход сепсиса у пациентов с различной коморбидностью, включая сердечно-сосудистые заболевания и сахарный диабет второго типа.Материалы и методы. В проспективное исследование включили 144 пациента ОРИТ двух клинических больниц г. Москвы в возрасте 18-75 лет с клиническими признаками сепсиса (СЕПСИС-3, 2016).Результаты. В группе пациентов с сердечно-сосудистой патологией носители генотипа TT AGTR1 rs275651 характеризовались меньшим уровнем летальности по сравнению с носителями аллеля A (25 летальных исходов из 33 против 16 из 16, соответственно, p=0,041, ТМФ; p=0,0019, log rank тест). В группе пациентов с сахарным диабетом (n=62), также обнаружили значимые различия в исходе сепсиса — в зависимости от варианта генотипа AGTR1 rs275651. В подгруппе носителей генотипа TT AGTR1 rs275651 выявили значимо меньшую летальность по сравнению с носителями генотипов ТА, AA (27 летальных исхода из 41 и 20 из 21 соответственно, p=0,012, ТМФ; OR=10,37; 95% CI: 1,26-85,5; p<0,0001, log rank тест).Заключение. Выявили связь функционального полиморфизма AGTR1 -777 T>A (rs275651) с исходом сепсиса у пациентов ОРИТ с высоким уровнем исходной коморбидности: у носителей более распространенного генотипа TT летальность ниже по сравнению с носителями минорной аллели A.

Blood pressure dysregulation and circulatory failure are major contributors to the progression of sepsis and especially septic shock. One of the genes affecting the vascular endothelium and arteriolar tone is the angiotensin II receptor 1 gene (AGTR1). The AGTR1 rs275651 single-nucleotide polymorphism is associated with the development of angina, high altitude pulmonary edema, and hypertension. The significance of the AGTR1 rs275651 polymorphism in sepsis, particularly in patients with significant comorbidity, has not been studied previously.The aim of the study was to determine the impact of AGTR1 functional polymorphism on sepsis outcome in patients with various comorbidities, including cardiovascular disease and type 2 diabetes mellitus.Material and methods. A prospective study included 144 ICU patients of two clinical hospitals in Moscow, aged 18-75 years with clinical signs of sepsis (Sepsis-3, 2016).Results. In the group of patients with cardiovascular diseases, carriers of the TT AGTR1 rs275651 genotype had a lower mortality rate compared with carriers of the A allele (25 deaths out of 33 versus 16 out of 16, respectively, P=0.041, Fisher's exact test; P=0.0019, log-rank test). In the group of patients with diabetes mellitus (n=62), we also found significant differences in sepsis outcome based on the AGTR1 rs275651 genotype variant. The subgroup of TT AGTR1 rs275651 genotype carriers demonstrated significantly lower mortality compared with TA, AA genotypes carriers (27 deaths out of 41 and 20 out of 21, respectively, P=0.012, Fisher's exact test; OR=10.37; 95% CI: 1.26 to 85.5; P<0.0001, log-rank test).Conclusion. We found an association of the functional polymorphism AGTR1 -777 T>A (rs275651) with sepsis outcome in ICU patients with high-value baseline comorbidity: carriers of the more common TT genotype had lower mortality compared to carriers of the minor A allele.

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