Investigation of paraoxonase1 enzyme activity and Q/R 192 polymorphism in severe COVID-19 cases

Öz

COVID-19, an infection associated with numerous cases and deaths globally since 2019, has been a subject of extensive research. Paraoxonase1 (PON1), recognized for its antioxidant activity and contribution to the reduction of oxidative damage, is the focus of this study. The research aims to measure the activity of the human serum PON1 enzyme with detoxification and antioxidant properties in COVID-19 cases leading to pneumonia. Additionally, the phenotype of the PON1 Q/R 192 polymorphism is investigated and compared with a control group. The study includes 26 severe COVID-19 cases and 24 healthy individuals. The phenotype distribution of patients is determined as 38.48% QQ, 53.83% QR, and 7.69% RR, while in the control group, these percentages are 50.00% QQ, 29.17% QR, and 20.83% RR. Furthermore, PON1 activity is measured in 26 COVID-19 patients and 24 healthy individuals. The results indicate distinct differences in the phenotype distribution of the PON1 Q/R 192 polymorphism between COVID-19 patients and the control group. The percentages of QQ, QR, and RR are unique in both groups. Additionally, PON1 activity is measured, revealing that the control group exhibits higher PON1 activity compared to the affected individuals.

Anahtar Kelimeler

• Paraoxonase1
• SARS-COV-2
• COVID-19
• Q/R 192R polymorphism

Ağır COVID-19 geçiren hastalarda paraoksonaz1 enzim aktivitesinin ve Q/R 192 polimorfizminin araştırılması

Öz

COVID-19, 2019 yılından bu yana dünya genelinde çok sayıda vaka ve ölümle ilişkilendirilen bir enfeksiyon olup, kapsamlı araştırmalara konu olmuştur. Antioksidan aktivitesi ve oksidatif hasarın azaltılmasına katkısı ile bilinen Paraoksonaz1 (PON1), bu çalışmanın odak noktasını oluşturmaktadır. Araştırma, zatürreye yol açan COVID-19 vakalarında detoksifikasyon ve antioksidan özelliklere sahip insan serum PON1 enziminin aktivitesini ölçmeyi amaçlamaktadır. Ayrıca, PON1 Q/R 192 polimorfizminin fenotipi incelenmiş ve bir kontrol grubu ile karşılaştırılmıştır. Çalışma, 26 ağır COVID-19 vakası ve 24 sağlıklı bireyi içermektedir. Hastaların fenotip dağılımı %38,48 QQ, %53,83 QR ve %7,69 RR olarak belirlenirken, kontrol grubunda bu oranlar sırasıyla %50,00 QQ, %29,17 QR ve %20,83 RR olarak bulunmuştur. Bunun yanı sıra, 26 COVID-19 hastası ve 24 sağlıklı bireyde PON1 aktivitesi ölçülmüştür. Sonuçlar, COVID-19 hastaları ile kontrol grubu arasında PON1 Q/R 192 polimorfizminin fenotip dağılımında belirgin farklılıklar olduğunu göstermektedir. QQ, QR ve RR yüzdeleri her iki grupta da benzersizdir. Ayrıca, PON1 aktivitesi ölçümleri, kontrol grubunun etkilenen bireylere kıyasla daha yüksek PON1 aktivitesi sergilediğini ortaya koymaktadır.

Anahtar Kelimeler

• Paraoksonaz1
• SARS-COV-2
• COVID-19
• Q/R 192R polimorfizim

Kaynakça

1. Velavan, T.P. and Meyer, C.G., The COVID-19 epidemic., Tropical Medicine & International Health : TM & IH, 25, 3, 278–280, (2020).
2. Nalbandian, A., Sehgal, K., Gupta, A., Madhavan, M.V, McGroder, C., et al., Post-acute COVID-19 syndrome., Nature Medicine, 27, 4, 601–615, (2021).
3. Guan, C.S., Lv, Z. Bin, Yan, S., Du, Y.N., Chen, H., et al., Imaging Features of Coronavirus disease 2019 (COVID-19): Evaluation on Thin-Section CT., Academic Radiology, 27, 5, 609–613, (2020).
4. Rodríguez-Tomàs, E., Iftimie, S., Castañé, H., Baiges-Gaya, G., Hernández-Aguilera, A., et al., Clinical Performance of Paraoxonase-1-Related Variables and Novel Markers of Inflammation in Coronavirus Disease-19. A Machine Learning Approach., Antioxidants (Basel, Switzerland), 10, 6, (2021).
5. Medina-Díaz, I.M., Ponce-Ruíz, N., Rojas-García, A.E., Zambrano-Zargoza, J.F., Bernal-Hernández, Y.Y., et al., The Relationship between Cancer and Paraoxonase 1., Antioxidants (Basel, Switzerland), 11, 4, (2022).
6. Hussain, T., Tan, B., Yin, Y., Blachier, F., Tossou, M.C.B., et al., Oxidative stress and inflammation: what polyphenols can do for us?, Oxidative Medicine and Cellular Longevity, 2016, 1, 7432797, (2016).
7. Kattoor, A.J., Pothineni, N.V.K., Palagiri, D., and Mehta, J.L., Oxidative stress in atherosclerosis, Current Atherosclerosis Reports, 19, 1–11, (2017).
8. Rendra, E., Riabov, V., Mossel, D.M., Sevastyanova, T., Harmsen, M.C., et al., Reactive oxygen species (ROS) in macrophage activation and function in diabetes, Immunobiology, 224, 2, 242–253, (2019).

9. Delgado-Roche, L. and Mesta, F., Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection, Archives of Medical Research, 51, 5, 384–387, (2020).
10. Uysal, S., Akyol, S., Hasgül, R., Armutcu, F., and Yiğitoğlu, M.R., Çok yönlü bir enzim: Paraoksonaz, Yeni Tıp Dergisi, 28, 3, 136–141, (2011).
11. Kilic, S.S., Serum arylesterase and paraoxonase activity in patients with chronic hepatitis, World Journal of Gastroenterology, 11, 46, 7351, (2005).
12. Wang, F.-S., Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection, World Journal of Gastroenterology, 9, 4, 641, (2003).
13. Mackness, B., Durrington, P.N., and Mackness, M.I., Human Serum Paraoxonase, General Pharmacology, 31, 3, 329–336, (1998).
14. Dantoine, T.F., Drouet, M., Debord, J., Merle, L., Cogne, M., et al., Paraoxonase 1 192/55 gene polymorphisms in Alzheimer’s disease, Annals of the New York Academy of Sciences, 977, 1, 239–244, (2002).
15. Durrington, P.N., Mackness, B., and Mackness, M.I., Paraoxonase and atherosclerosis, Arteriosclerosis, Thrombosis, and Vascular Biology, 21, 4, 473–480, (2001).
16. La Du, B.N., Aviram, M., Billecke, S., Navab, M., Primo-Parmo, S., et al., On the physiological role(s) of the paraoxonases, Chemico-Biological Interactions, 119–120, 379–388, (1999).
17. Kotur-Stevuljevic, J., Spasic, S., Jelic-Ivanovic, Z., Spasojevic-Kalimanovska, V., Stefanovic, A., et al., PON1 status is influenced by oxidative stress and inflammation in coronary heart disease patients., Clinical Biochemistry, 41, 13, 1067–1073, (2008).
18. Saadat, M., Prevalence and mortality of COVID-19 are associated with the L55M functional polymorphism of Paraoxonase 1, Proceedings of Singapore Healthcare, 31, 20101058211040584, (2022).
19. Eckerson, H.W., Wyte, C.M., and La Du, B.N., The human serum paraoxonase/arylesterase polymorphism., American Journal of Human Genetics, 35, 6, 1126, (1983).
20. La Du, B.N. and Eckerson, H.W., The polymorphic paraoxonase/arylesterase isozymes of human serum., Federation Proceedings, 43, 8, 2338–2341, (1984).
21. Ammar, A., Chtourou, H., Boukhris, O., Trabelsi, K., Masmoudi, L., et al., COVID-19 home confinement negatively impacts social participation and life satisfaction: a worldwide multicenter study, International Journal of Environmental Research and Public Health, 17, 17, 6237, (2020).
22. Mackness, M.I., Mackness, B., Arrol, S., Wood, G., Bhatnagar, D., et al., Presence of paraoxonase in human interstitial fluid, FEBS Letters, 416, 3, 377–380, (1997).
23. Nie, Y., Luo, D., Yang, M., Wang, Y., Xiong, L., et al., A meta-analysis on the relationship of the PON genes and Alzheimer disease, Journal of Geriatric Psychiatry and Neurology, 30, 6, 303–310, (2017).
24. Hofer, S.E., Bennetts, B., Chan, A.K., Holloway, B., Karschimkus, C., et al., Association between PON 1 polymorphisms, PON activity and diabetes complications, Journal of Diabetes and Its Complications, 20, 5, 322–328, (2006).
25. Furlong, C.E., Marsillach, J., Jarvik, G.P., and Costa, L.G., Paraoxonases-1, -2 and -3: What are their functions?, Chemico-Biological Interactions, 259, 51–62, (2016).
26. Bacchetti, T., Ferretti, G., and Sahebkar, A., The role of paraoxonase in cancer, Seminars in Cancer Biology, 56, October, 72–86, (2019).
27. Sarioglu, N., Bilen, C., Cevik, C., and Gencer, N., Paraoxonase activity and phenotype distribution in patients with chronic obstructive pulmonary disease, Eurasian Journal of Medicine, 52, 2, 161–165, (2020).
28. Ghoreshi, Z.-A.-S., Abbasi-Jorjandi, M., Asadikaram, G., Sharif-Zak, M., Seyedi, F., et al., Paraoxonase 1 rs662 polymorphism, its related variables, and COVID-19 intensity: Considering gender and post-COVID complications, Experimental Biology and Medicine, 15353702221128564, (2022).
29. Kaman, D., İlhan, N., Metin, K., Akbulut, M., and Üstündağ, B., A preliminary study of human paraoxonase and PON 1 L/M55–PON 1 Q/R 192 polymorphisms in Turkish patients with coronary artery disease, Cell Biochemistry and Function, 27, 2, 88–92, (2009).
30. Stafford, M., Boolaky, U., Elwell-Sutton, T., Asaria, M., and Nazroo, J., How to interpret research on ethnicity and COVID-19 risk and outcomes: five key questions, (2020).
31. Akyuva, Y., Nur, G., Deveci, H.A., and Kocabas Guler, S., Oxidative stress and biochemical alterations in patients with head and multiple organ traumas, Turkish Neurosurgery, 33, 5, 855–861, (2023).
32. Deveci, H.A., Nur, G., Cicek, H., and Karapehlivan, M., Evaluation of oxidative stress factors in patients with osteoporosis, Medicine Science, 6, 3, 479–482, (2017).
33. Deveci, H.A., Nur, G., Alpay, M., and Özmerdivenli, R., Levels of paraoxonase, high-density lipoprotein and total sialic acid levels in patients with polycystic ovary syndrome, Journal of Cellular Neuroscience and Oxidative Stress, 9, 2, 630–636, (2017).
34. Ergün, A., Yüksel, H., Arslan, M., and Arslan, O., Investigation of the effects of some drugs on sheep Paraoxonase-1, Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 25, 2, 483–488, (2023).
35. Erzengin, M., Demir, D., Arslan, M., and Sinan, S., Purification and characterization of paraoxonase 1 (PON1) from Swiss Black, Holstein, and Montofon bovines, Applied Biochemistry and Biotechnology, 173, 7, 1597–1606, (2014).