The Relationship Between IL8/CXCL8 Gene Polymorphism and the Severity of COVID-19
Year 2023,
, 142 - 147, 31.08.2023
Güneş Çakmak Genç
,
Begüm Beril Yalçın
,
Emre Horuz
,
Sevim Karakaş Çelik
,
Ahmet Dursun
Abstract
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.
References
- 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.
IL8/CXCL8 Gen Polimorfizminin COVID-19 Şiddeti ile İlişkisi
Year 2023,
, 142 - 147, 31.08.2023
Güneş Çakmak Genç
,
Begüm Beril Yalçın
,
Emre Horuz
,
Sevim Karakaş Çelik
,
Ahmet Dursun
Abstract
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.
References
- 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.