ارتباط بین پلی‌مورفیسم تک‌نوکلئوتیدی-174 G/C اینترلوکین-6 با شدت بیماری کووید-19

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه ایمونولوژی، دانشکده پزشکی، دانشگاه شاهد، تهران، ایران

2 مرکز تحقیقات تنظیم پاسخ‌های ایمنی، دانشگاه شاهد، تهران، ایران

3 گروه تخصصی ژنتیک مولکولی، دانشکده علوم پایه، دانشگاه آزاد اسلامی، واحد علوم و تحقیقات، تهران، ایران

4 مرکز تحقیقات بیماری های غیرواگیر، دانشگاه علوم پزشکی فسا، فسا، ایران

چکیده

مقدمه و هدف: اینترلوکین-6 یکی از سایتوکاین‌هایی است که افزایش و نقش آن در پاتوژنز کووید-19 در مطالعات مختلف گزارش شده است. غلظت اینترلوکین-6 تحت تأثیر چندین عامل محیطی و ژنتیکی، ازجمله مکان‌های پلی‌مورفیک در ژن IL-6 قرار می‌گیرد. در مطالعه حاضر، پلی‌مورفیسم rs1800795 که در ناحیه ژنی IL6 قرار دارد مورد بررسی قرار گرفت.
مواد و روش ها: افراد شرکت کننده در این مطالعه به دو گروه سرپایی (245 نفر) و بستری (245 نفر) به علت ابتلا به COVID-19 تقسیم شدند. نمونه خون محیطی از بیماران تهیه و DNA آن‌ها استخراج شد، سپس ژنوتیپ پلی‌مورفیسم rs1800795 به وسیله روش Tetra Arms PCR مورد سنجش قرار گرفت. تجزیه و تحلیل داده‌ها با استفاده از نرم افزار SPSS و آزمون‌های آماری کای دو، تی تست و رگرسیون لجستیک صورت گرفت.
نتایج: میانگین سن بیماران در گروه سرپایی3/12±6/41 سال ولی در گروه بیماران بستری، 1/17±0/61 سال بود (P-value<0.001)؛ همچنین فراوانی افراد سیگاری و بیماران دچار مشکلات کلیوی (P-value<0.05) و همینطور بیماران مبتلا به فشار خون, دیابت ملیتوس و دارای سابقه بیماری قلبی (P-value<0.001) در گروه‌های سرپایی و بستری اختلاف معنی‌داری داشت. از نظر فراوانی افراد دارای آلل G در گروه بستری به صورت معنی‌داری کمتر از گروه‌ سرپایی           (P-value= 0.045) بود.
نتیجه‌گیری: فراوانی واریانت‌های پلی‌مورفیسم rs1800795 اینترلوکین-6 در گروه‌های مختلف بیماران کووید-19 با شدت علائم بالینی متفاوت، با یکدیگر تفاوت دارد و احتمالا آلل G می‌تواند نقش حفاظت کننده‌ای در برابر بیماری COVID-19 داشته باشد.

کلیدواژه‌ها


عنوان مقاله [English]

Association between interleukin-6-174G/C single nucleotide polymorphism with the COVID-19 severity

نویسندگان [English]

  • Bahman Rahimlou 1
  • Sara Ghaffarpour 2
  • Mohammad Saber Zamani 3
  • Mohammad Mahdi Naghizadeh 4
  • Tooba Ghazanfari 2
1 Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran
2 Immunoregulation Research Center, Shahed University, Tehran, Iran
3 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
4 Non-communicable Diseases Research Center, Fasa University of Medical Science, Fasa, Iran
چکیده [English]

Background and Objective: Interleukin-6 is one of the cytokines whose increase and role in the pathogenesis of Covid-19 has been reported in various studies. Interleukin-6 affects environmental factors and genes, including polymorphic sites in the IL-6 gene. In the present study, the rs1800795 polymorphism located in the IL6 gene region was investigated.
Materials and Methods: Participants in this study were divided into outpatient (n=245) and inpatient (n=245) groups due to COVID-19. Peripheral blood samples were taken from patients and their DNA was extracted, then rs1800795 polymorphism genotype was measured by Tetra Arms PCR. Data were analyzed using SPSS software and Chi-Square and t-test students.
Results: The mean age of patients in the outpatient group was        41.6±12.3 years but in the inpatient group was 61±17.1 years (P-value <0.001); There was also a significant difference in the frequency of smokers and patients with kidney problems (P-value <0.05) as well as patients with hypertension, diabetes mellitus and a history of heart disease (P-value <0.001) in outpatient and inpatient groups. The frequency of G alleles in the inpatient group was significantly lower than the outpatient group (P-value = 0.045).
Conclusion: The frequency of polymorphism variants of rs1800795 interleukin-6 varies in different groups of Covid-19 patients with varying degrees of clinical symptoms, and the G allele may possibly play a protective role against COVID-19.

کلیدواژه‌ها [English]

  • Covid-19
  • Polymorphism
  • Interleukin-6
  • rs1800795
  1. Millán-Oñate J, Rodriguez-Morales AJ, Camacho-Moreno G, Mendoza-Ramírez H, Rodríguez-Sabogal IA, Álvarez-Moreno CJI. A new emerging zoonotic virus of concern: the 2019 novel Coronavirus (SARS CoV-2). 2020;24(3):187-92.
  2. Fan W, Su Z, Bin Y, Yan-Mei C, Wen W, Zhi-Gang S, et al. Holmes Edward C., Zhang Yong-Zhen. A new coronavirus associated with human respiratory disease in China. Nature 2020;579(7798):265-9.
  3. Johnson NP, Mueller J. Updating the accounts: global mortality of the 1918-1920" Spanish" influenza pandemic. Bulletin of the History of Medicine 2002:105-15.
  4. Short KR, Kedzierska K, van de Sandt CE. Back to the future: lessons learned from the 1918 influenza pandemic. Frontiers in Cellular and Infection Microbiology 2018;8:343.
  5. Wu Z, McGoogan JMJJ. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention 2020;323(13):1239-42.
  6. Yang X, Yu Y, Xu J, Shu H, Liu H, Wu Y, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study 2020.
  7. Ruan Q, Yang K, Wang W, Jiang L, Song JJIcm. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China 2020;46(5):846-8.
  8. Rostamian A, Ghazanfari T, Arabkheradmand J, Edalatifard M, Ghaffarpour S, Salehi MR, et al. Interleukin-6 as a Potential Predictor of COVID-19 disease severity in hospitalized patients and its association with clinical laboratory routine tests. Immunoregulation 2020;3(1):29-36.
  9. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395(10223):497-506.
  10. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respiratory Medicine2020;8(4):420-2.
  11. Wu F, Zhao S, Yu B, Chen Y-M, Wang W, Song Z-G, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579(7798):265-9.
  12. Catanzaro M, Fagiani F, Racchi M, Corsini E, Govoni S, Lanni CJST, et al. Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Signal Transduction and Targeted Therapy2020;5(1):1-10.
  13. Kirtipal N, Bharadwaj SJJoBS, Dynamics. Interleukin 6 polymorphisms as an indicator of COVID-19 severity in humans. Journal of Biomolecular Structure and Dynamics 2021;12:1-4.
  14. Terry CF, Loukaci V, Green FRJJoBC. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. The Journal of Biological Chemistry 2000;275(24):18138-44.
  15. Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. Journal of Biological Chemistry 2000;275(24):18138-44.
  16. Babusikova E, Jurecekova J, Jesenak M, Evinova A. Association of gene polymorphisms in interleukin 6 in infantile bronchial asthma. Archivos de Bronconeumología (English Edition) 2017;53(7):381-6.
  17. Ulhaq ZS, Soraya GV. Anti-IL-6 receptor antibody treatment for severe COVID-19 and the potential implication of IL-6 gene polymorphisms in novel coronavirus pneumonia. Medicina Clinica 2020;155(12):548.
  18. Doyle WJ, Casselbrant ML, Li-Korotky H-S, Cullen Doyle AP, Lo C-Y, Turner R, et al. The interleukin 6− 174 C/C genotype predicts greater rhinovirus illness. The Journal of Infectious Diseases 2010;201(2):199-206.
  19. Riazalhosseini B, Mohamed Z, Apalasamy YD, Shafie NS, Mohamed R. Interleukin-6 gene variants are associated with reduced risk of chronicity in hepatitis B virus infection in a Malaysian population. Biomedical Reports 2018;9(3):213-20.
  20. Mao Z-R, Zhang S-L, Feng B. Association of IL-10 (-819T/C,-592A/C and-1082A/G) and IL-6-174G/C gene polymorphism and the risk of pneumonia-induced sepsis. Biomarkers 2017;22(2):106-12.
  21. Palumbo AA, Forte G, Pileri D, Vaccarino L, Conte F, D’Amelio L, et al. Analysis of IL-6, IL-10 and IL-17 genetic polymorphisms as risk factors for sepsis development in burned patients. Burns 2012;38(2):208-13.
  22. Jiménez-Sousa MA, Medrano LM, Liu P, Fernandez-Rodriguez A, Almansa R, Gomez-Sanchez E, et al. IL-6 rs1800795 polymorphism is associated with septic shock-related death in patients who underwent major surgery: a preliminary retrospective study. Annals of Intensive Care 2017;7(1):1-9.
  23. Shahin W, Abdel Meguid I, Elhamamsy K, Shaker O. IL6-174 G/C Gene Polymorphism in Children with Septicemia: Single Center Study. Journal of Pediatrics & Neonatal Care 2016;4(5):00156.
  24. Kerget F, Kerget B. Frequency of interleukin-6 rs1800795 (-174G/C) and rs1800797 (-597G/A) polymorphisms in COVID-19 patients in Turkey who develop macrophage activation syndrome. Japanese Journal of Infectious Diseases 2021:JJID. 2021.046.