Güneş ÇAKMAK GENÇ, Begüm Beril YALÇIN, Emre HORUZ, Sevim KARAKAŞ ÇELİK, Ahmet DURSUN

IL8/CXCL8 Gen Polimorfizminin COVID-19 Şiddeti ile İlişkisi

Amaç: COVID-19, ilk olarak yüksek ateş ve nefes darlığı ile tanımlanan, damlacık ve temas yoluyla bulaştığı bilinen, viral bir solunum yolu hastalığıdır. Hastalığın klinik seyri kişiden kişiye farklılık göstermektedir. COVID-19’un klinik seyrindeki farklılıklar komorbidite ve yaş gibi etkenlere bağlı olabilmekle birlikte, inflamatuar yanıttaki kişisel genetik farklılıklara da dayanabilir. Bu çalışmada COVID-19 hastalığının klinik şiddeti ile IL8/CXCL8 rs4073 gen polimorfizmi arasındaki ilişkiyi araştırmayı amaçladık. Gereç ve Yöntemler: Klinik şiddetine göre hafif, orta ve şiddetli olmak üzere üç gruba ayrılmış olan 150 COVID-19 hastasında, IL8/CXCL8 rs4073 (-251A/T) gen polimorfizmi polimeraz zincir reaksiyonu tabanlı restriksiyon parçası uzunluk polimorfizmi (PCR-RFLP) yöntemi ile belirlendi. Bulgular: Sonuçlarımız IL8/CXCL8 rs4073 gen polimorfizmi ile hastalık şiddeti arasında genotip ve alel sıklığı dağılımı açısından anlamlı bir fark olmadığını göstermiştir. Ancak klinik bulgular açısından değerlendirildiğinde T allelinin, pnömoni bulgusu olan COVID-19 vakalarında daha sık görülmesi T allelinin COVID-19’da pnömoni riskini 1,7 kat artırdığı belirlenmiştir. Sonuç: Bu çalışmadan elde edilen sonuçlar IL8/CXCL8 rs4073 gen polimorfizminin erken tedavi ve takip sayesinde hastalarda pnömoninin ilerlemesini engellemede kullanılabilecek bir belirteç adayı olabileceğini göstermiştir. Bunun için daha fazla sayıda hasta içeren büyük popülasyonlarda yapılmış yeni çalışmalara ihtiyaç vardır.

Anahtar Kelimeler:

COVID-19, SarsCOV-2, IL8, CXCL8, gen polimorfizmi, rs4073

The Relationship Between IL8/CXCL8 Gene Polymorphism and the Severity of COVID-19

Aim: COVID-19 is a viral respiratory disease primarily characterized by high fever and shortness of breath, known to be transmitted through droplets and contact. The clinical course of the disease varies from person to person. Differences in the clinical course of COVID-19 may be attributed to factors such as comorbidities, age, and could also be based on individual genetic variations in the inflammatory response. In this study, we aimed to investigate the relationship between the severity of clinical manifestations of COVID-19 and the IL8/CXCL8 rs4073 gene polymorphism. Material and Methods: The IL8/CXCL8 rs4073 (-251A/T) gene polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 150 COVID-19 patients who were classified into three groups based on the severity of their clinical manifestations: mild, moderate, and severe. Results: Our results demonstrated no significant difference in genotype and allele frequency distribution between the IL8/CXCL8 rs4073 gene polymorphism and disease severity. However, when evaluated in terms of clinical findings, the T allele was found to be more common in COVID-19 cases with pneumonia symptoms, and it was determined that the T allele increased the risk of pneumonia in COVID-19 by 1.7 times. Conclusion: The findings from this study suggest that the IL8/CXCL8 rs4073 gene polymorphism could serve as a potential marker that, through early treatment and monitoring, could help prevent the progression of pneumonia in patients. Further studies with larger populations, involving a greater number of patients, are needed to validate these findings.

Keywords:

COVID-19, SarsCOV-2, IL8, CXCL8, gene polymorphism, rs4073,

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1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382(8):727- 733.
2. Benvenuto D, Giovanetti M, Ciccozzi A, Spoto S, Angeletti S, Ciccozzi M. The 2019-new coronavirus epidemic: Evidence for virus evolution. J Med Virol. 2020;92(4):455-459.
3. Ravi N, Cortade DL, Ng E, Wang SX. Diagnostics for SARSCoV- 2 detection: A comprehensive review of the FDAEUA COVID-19 testing landscape. Biosens Bioelectron. 2020;165:112454.
4. Honore PM, Barreto Gutierrez L, Kugener L, Redant S, Attou R, Gallerani A, De Bels D. Inhibiting IL-6 in COVID-19: we are not sure. Crit Care. 2020;24(1):463.
5. Palanques-Pastor T, López-Briz E, Poveda Andrés JL. Involvement of interleukin 6 in SARS-CoV-2 infection: siltuximab as a therapeutic option against COVID-19. Eur J Hosp Pharm. 2020;27(5):297-298.
6. Atlante S, Mongelli A, Barbi V, Martelli F, Farsetti A, Gaetano C. The epigenetic implication in coronavirus infection and therapy. Clin Epigenetics. 2020;12(1):156.
7. Fara A, Mitrev Z, Rosalia RA, Assas BM. Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines. Open Biol. 2020;10(9):200160.
8. Cesta MC, Zippoli M, Marsiglia C, Gavioli EM, Mantelli F, Allegretti M, Balk RA. The Role of Interleukin-8 in Lung Inflammation and Injury: Implications for the Management of COVID-19 and Hyperinflammatory Acute Respiratory Distress Syndrome. Front Pharmacol. 2022;12:808797.
9. Ahluwalia TS, Khullar M, Ahuja M, Kohli HS, Bhansali A, Mohan V, Venkatesan R, Rai TS, Sud K, Singal PK. Common variants of inflammatory cytokine genes are associated with risk of nephropathy in type 2 diabetes among Asian Indians. PLoS One. 2009;4(4):e5168.
10. Mukaida N, Shiroo M, Matsushima K. Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989;143(4):1366-71.
11. Hull J, Thomson A, Kwiatkowski D. Association of respiratory syncytial virus bronchiolitis with the interleukin 8 gene region in UK families. Thorax. 2000;55(12):1023-7.
12. Lee WP, Tai DI, Lan KH, Li AF, Hsu HC, Lin EJ, Lin YP, Sheu ML, Li CP, Chang FY, Chao Y, Yen SH, Lee SD. The -251T allele of the interleukin-8 promoter is associated with increased risk of gastric carcinoma featuring diffuse-type histopathology in Chinese population. Clin Cancer Res. 2005;11(18):6431-41.
13. Li L, Li J, Gao M, Fan H, Wang Y, Xu X, Chen C, Liu J, Kim J, Aliyari R, Zhang J, Jin Y, Li X, Ma F, Shi M, Cheng G, Yang H. Interleukin-8 as a Biomarker for Disease Prognosis of Coronavirus Disease-2019 Patients. Front Immunol. 2021;11:602395.
14. Kashyap A, Sebastian SA, Krishnaiyer NarayanaSwamy SR, Raksha K, Krishnamurthy H, Krishna B, D’Souza G, Idiculla J, Vyas N. Molecular markers for early stratification of disease severity and progression in COVID-19. Biol Methods Protoc. 2022;7(1):bpac028.
15. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
16. https://www.covid19treatmentguidelines.nih.gov/ (accesed at 03.04.2023).
17. Georgitsi MD, Vitoros V, Panou C, Tsangaris I, Aimoniotou E, Gatselis NK, Chasou E, Kouliatsis G, Leventogiannis K, Velissaris D, Belesiotou E, Dioritou-Aggaliadou O, Giannitsioti E, Netea MG, Giamarellos-Bourboulis EJ, Giannikopoulos G, Alexiou Z, Voloudakis N, Koutsoukou A; Hellenic Sepsis Study Group. Individualized significance of the -251 A/T single nucleotide polymorphism of interleukin-8 in severe infections. Eur J Clin Microbiol Infect Dis. 2016;35(4):563-70.
18. Matheson MC, Ellis JA, Raven J, Walters EH, Abramson MJ. Association of IL8, CXCR2 and TNF-alpha polymorphisms and airway disease. J Hum Genet. 2006;51(3):196-203.
19. Strieter RM. Interleukin-8: a very important chemokine of the human airway epithelium. Am J Physiol Lung Cell Mol Physiol. 2002;283(4):L688-9.
20. Lowe PR, Galley HF, Abdel-Fattah A, Webster NR. Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients. Crit Care Med. 2003;31(1):34-8.
21. Regel G, Grotz M, Weltner T, Sturm JA, Tscherne H. Pattern of organ failure following severe trauma. World J Surg. 1996;20(4):422-9.
22. Hildebrand F, Stuhrmann M, van Griensven M, Meier S, Hasenkamp S, Krettek C, Pape HC. Association of IL-8-251A/T polymorphism with incidence of Acute Respiratory Distress Syndrome (ARDS) and IL-8 synthesis after multiple trauma. Cytokine. 2007;37(3):192-9.
23. Zhao XF, Zhu SY, Hu H, He CL, Zhang Y, Li YF, Wu YQ. [Association between interleukin-8 rs4073 polymorphisms and susceptibility to neonatal sepsis]. Zhongguo Dang Dai Er Ke Za Zhi. 2020;22(4):323-327.