Association of polymorphic variants of hemostatic system genes with the course of COVID-19

Cover Page

Cite item

Full Text

Abstract

Introduction.  COVID-19 is characterized by a varied clinical course.

The aim of the work was to identify associations of SNPs of hemostatic system genes with COVID-19.

Materials and methods. DNA was isolated from patients (n=117) and healthy participants (n=104). All infected patients were divided into 3 groups, depending on disease severity assessment, which was appreciated by NEWS2. Another group consisted of participants, who had asymptomatic infection in the past. Determination of SNPs of the genes FGB (-455 G/A), FII (20210 G/A), FV (1691 G/A), FVII (10976 G/A), FXIIIA1 (103 G/T), ITGA2 (807 C/T), ITGB3 (1565 T/C), SERPINE1 (-675 5G/4G) were performed by PCR using the “Genetics of Hemostasis” kit (“DNA-Technology”, Russia).

Results. In analyzed SNPs, no significant differences were detected between the group of infected patients and healthy participants. But significant association was revealed in gene SERPINE1 (-675 5G/4G), when patient groups, differing in the disease severity, were analyzed relative to the group of participants with asymptomatic infection (p=0.0381; p=0 .0066; p=0.0009). It was found, that as COVID-19 severity scores increased, the proportion of 5G allele of gene SERPINE1 decreased, and the proportion of the 4G allele increased (p=0.005; p=0.009; p=0.0005). Similar processes were observed for genotypes 5G/5G and 4G/4G.

Discussion. The gene SERPINE1 (-675 5G/4G) is associated with the severity of COVID-19.

Conclusion. For the first time, it was discovered that 5G/5G genotype of gene SERPINE1 (-675 5G/4G) can be a marker of a milder course of COVID-19, and the 4G/4G genotype as a more severe one.

About the authors

Lyudmila I. Nikolaeva

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Author for correspondence.
Email: l.i.nikolaeva@mail.ru
ORCID iD: 0000-0002-1323-5568

D.Sci. in Biology, Leading Researcher of the Laboratory Gene Engineering Products

Russian Federation, 123098, Moscow

Maya D. Stuchinskaya

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: mayastaya@mail.ru
ORCID iD: 0000-0001-8544-7482

junior researcher of the Laboratory Gene Engineering Products

Russian Federation, 123098, Moscow

Anna V. Dedova

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: dedova.anna2010@mail.ru
ORCID iD: 0000-0002-2491-9324

graduate student of the Laboratory Gene Engineering Products

Russian Federation, 123098, Moscow

Shevchenko G. Nadezhda

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: dr.nadya@inbox.ru
ORCID iD: 0000-0002-2486-4554

junior researcher of the Laboratory Gene Engineering Products

Russian Federation, 123098, Moscow

Irina N. Khlopova

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: khlopova.ira@yandex.ru
ORCID iD: 0000-0002-7419-590X

C.Sci. in Medicine, leading researcher of the Laboratory chronic viral infections

Russian Federation, 123098 Moscow

Irina S. Kruzhkova

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia; Infection Diseases Clinical Hospital Number 1, Moscow Department of Health

Email: irina-kru@yandex.ru
ORCID iD: 0000-0002-1983-481X

researcher of the Laboratory respiratory viral infections with drug testing

Russian Federation, 123098 Moscow; 125367, Moscow

Lilya N. Merkulova

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: merkulova0320@yandex.ru
ORCID iD: 0000-0002-7260-0879

C.Sci. in Medicine, leading researcher of the Laboratory respiratory of the viral infections with drug testing

Russian Federation, 123098, Moscow

Lidya B. Kisteneva

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: lborisovna2007@yandex.ru
ORCID iD: 0000-0001-7336-409X

D.Sci. in Medicine, leading researcher of the Laboratory chronic viral infections

Russian Federation, 123098, Moscow

Lyudmila V. Kolobukhina

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia; Infection Diseases Clinical Hospital Number 1, Moscow Department of Health

Email: lkolobuchina@yandex.ru
ORCID iD: 0000-0001-5775-3343

D.Sci. in Medicine, leading researcher of the Laboratory respiratory viral infections with drug testing

Russian Federation, 123098 Moscow; 125367, Moscow

Evgenya A. Mukasheva

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: mukasheva_evgeniya@mail.ru
ORCID iD: 0000-0002-5688-5309

researcher of the Laboratory of Influenza Etiology and Epidemiology

Russian Federation, 123098, Moscow

Kirill G. Krasnoslobodtsev

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: kkg_87@mail.ru
ORCID iD: 0000-0003-1745-9128

researcher of the Laboratory of Influenza Etiology and Epidemiology

Russian Federation, 123098, Moscow

Svetlana V. Trushakova

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: s.trushakova@gmail.com
ORCID iD: 0000-0002-9610-3041

C.Sci. in Biology, senior researcher of the Laboratory of Influenza Etiology and Epidemiology

Russian Federation, 123098, Moscow

Anastasia S. Krepkaya

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: nastya18-96@mail.ru
ORCID iD: 0000-0002-7272-4011

junior researcher of the Laboratory of Influenza Etiology and Epidemiology

Russian Federation, 123098, Moscow

Victor V. Kuprianov

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: vkoup@mail.ru
ORCID iD: 0000-0002-8602-1974

C.Sci. in Biology, senior researcher of the Laboratory Gene Engineering Products

Russian Federation, 123098, Moscow

Natalia A. Nikitenko

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: nan-nikitenko@yandex.ru
ORCID iD: 0000-0001-5829-744X

C.Sci. in Biology, senior researcher of the Cell Microbiology Laboratory

Russian Federation, 123098, Moscow

Elizaveta A. Khadorich

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: eli.hadd@yandex.ru
ORCID iD: 0009-0005-1816-0496

laboratory assistant of the Cell Microbiology Laboratory

Russian Federation, 123098, Moscow

Egor M. Burmistrov

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: burmistrov.gamaleya@yandex.ru
ORCID iD: 0000-0002-6592-8331

researcher of the Cell Microbiology Laboratory

Russian Federation, 123098, Moscow

Igor N. Tyurin

Infection Diseases Clinical Hospital Number 1, Moscow Department of Health

Email: tyurin.dti@yandex.ru
ORCID iD: 0000-0002-5696-1586

C.Sci. in Medicine, Chief Physician, Infection Diseases Clinical Hospital No 1, Moscow Department of Health

Russian Federation, 125367, Moscow

Natalia A. Antipyat

Infection Diseases Clinical Hospital Number 1, Moscow Department of Health

Email: natadoc70@bk.ru
ORCID iD: 0000-0001-8578-2838

Deputy Chief Physician for Medical Affairs, Infection Diseases Clinical Hospital No 1, Moscow Department of Health

Russian Federation, 125367, Moscow

Elena I. Burtseva

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia

Email: elena-burtseva@yandex.ru
ORCID iD: 0000-0003-2518-6801

D.Sci. in Medicine, Head of the Laboratory of Influenza Etiology and Epidemiology

Russian Federation, 123098, Moscow

References

  1. Hui D.S., Azhar E.I., Madani T.A., Ntoumi F., Kock R., Dar O., et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health – The latest 2019 novel coronavirus outbreak in Wuhan, China. Int. J. Infect. Dis. 2020; 91: 264–66. https://doi.org/10.1016/j.ijid.2020.01.009
  2. Chen Y., Lio Q., Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J. Med. Virol. 2020; 92(4): 418–23. https://doi.org/10.1002/jmv.25681
  3. Connors J.M., Levy J.H. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020; 135(23): 2033–40. https://doi.org/10.1182/blood.2020006000
  4. Dolhnikoff M., Duarte-Neto A.N., de Almeida Monteiro R.A., da Silva L.F.F., de Oliveira E.P., Saldiva P.H.N., et al. Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19. J. Thromb. Haemost. 2020; 18(6): 1517–9. https://doi.org/10.1111/jth.14844
  5. Varga Z., Flammer A.J., Steiger P., Haberecker M., Andermatt R., Zinkernagel A.S., et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020; 395(10234): 1417–8. https://doi.org/10.1016/S0140-6736(20)30937-5
  6. Arachchillage D.R.J., Laffan M. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost. 2020; 18(5): 1233–4. https://doi.org/10.1111/jth.14820
  7. Gupta A., Madhavan M.V., Sehgal K., Nair N., Mahajan S., Sehrawat T.S., et al. Extrapulmonary manifestations of COVID-19. Nat. Med. 2020; 26(7): 1017–32. https://doi.org/10.1038/s41591-020-0968-3.
  8. Baranova A., Cao H., Zhang F. Unraveling risk genes of COVID-19 by multi-omics integrative analyses. Front. Med. (Lausanne). 2021; 8: 738687. https://doi.org/10.3389/fmed.2021.738687
  9. Saponi-Cortes J.M.R., Rivas M.D., Calle-Alonso F., Sanchez J.F., Costo A., Martin C., et al. IFNL4 genetic variant can predispose to COVID-19. Sci. Rep. 2021; 11(1): 21185. https://doi.org/10.1038/s41598-021-00747-z
  10. Samadizadeh S., Masoudi M., Rastegar M., Salimi V., Shahbaz M.B., Tahamtan A. COVID-19: why does disease severity vary among individuals? Respir. Med. 2021; 180: 106356. https://doi.org/10.1016/j.rmed.2021.106356
  11. Pairo-Castineira E., Rawlik K., Bretherick A.D., Qi T., Wu Y., Nassiri I., et al. GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19. Nature. 2023; 617(7962): 764–8. https://doi.org/10.1038/s41586-023-06034-3
  12. Chen J.Y., Zhai C.N., Wang Z.Q., Li R., Wu W.J., Hou K., et al. The susceptibility of SERPINE1 rs1799889 SNP in diabetic vascular complications: a meta-analysis of fifty-one case-control studies. BMC Endocr. Disord. 2021; 21(1): 195. https://doi.org/10.1186/s12902-021-00837-z
  13. Gils A., Declerck P.J. Plasminogen activator inhibitor-1. Curr. Med. Chem. 2004; 11(17): 2323–34. https://doi.org/10.2174/0929867043364595
  14. Zhang Q., Jin Y., Li X., Peng X., Peng N., Song J. Plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphisms and risk of venous thromboembolism – a meta-analysis and systematic review. Vasa. 2020; 49(2): 141–6. https://doi.org/10.1024/0301-1526/a000839
  15. Huang X., Li Y., Huang Z., Wang C.., Xu Z. PAI-1 gene variants and COC use are associated with stroke risk: a case-control study in the Han Chinese women. J. Mol. Neurosci. 2014; 54(4): 803–10. https://doi.org/10.1007/s12031-014-0418-0
  16. Gao W.F., Guo Y.B., Bai Y., Ding X.Y., Yan Y.J., Wu ZQ. Association between PAI-1 4G/5G polymorphism and diabetic nephropathy: a meta-analysis in the Chinese population. Int. Urol. Nephrol. 2016; 48(9): 1483–9. https://doi.org/10.1007/s11255-016-1333-9
  17. Wang S., Cao Q., Wang X., Li B., Tang M., Yuan W., et al. PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis. PLoS One. 2013; 8(2): e56797. https://doi.org/10.1371/journal.pone.0056797.
  18. Madàch K., Aladzsity I., Szilàgyi A., Fust G., Gàl J., Pénzes I., et al. 4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study. Crit. Care. 2010; 14(2): R79. https://doi.org/10.1186/cc8992
  19. Wang Z., Kong L., Luo G., Zhang H., Sun F., Liang W., et al. Clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with venous thromboembolism. Thromb. J. 2022; 20(1): 68. https://doi.org/10.1186/s12959-022-00430-x
  20. Li W., Mao S., Wu L., Shi W., Zhang J., Wang Z. Association between the PAI-1 4G/5G gene polymorphism and the risk of systemic lupus erythematosus/lupus nephritis. Crit. Rev. Eukaryot. Gene Expr. 2019; 29(1): 85–94. https://doi.org/10.1615/critreveukaryotgeneexpr.2019025311
  21. Kong M., Zhang H., Cao X., Lu Z. Higher level of neutrophil-to-lymphocyte is associated with severe COVID-19. Epidemiol. Infect. 2020; 148: e139. https://doi.org/10.1017/S0950268820001557
  22. Gorodin V.N., Moysova D.P., Zotov S.V., Vanyukov A.A., Podsadnaya A.A., Tikhonenko Yu.V. Role of polymorphisms of genes involved in hemostasis in COVID-19 pathogenesis. Infektsionnye bolezni. 2021; 19(2): 16–26. https://doi.org/10.20953/1729-9225-2021-2-16-26 https://elibrary.ru/cooovc (in Russian)

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2023 Nikolaeva L.I., Stuchinskaya M.D., Dedova A.V., Nadezhda S.G., Khlopova I.N., Kruzhkova I.S., Merkulova L.N., Kisteneva L.B., Kolobukhina L.V., Mukasheva E.A., Krasnoslobodtsev K.G., Trushakova S.V., Krepkaya A.S., Kuprianov V.V., Nikitenko N.A., Khadorich E.A., Burmistrov E.M., Tyurin I.N., Antipyat N.A., Burtseva E.I.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».