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Investigation of the Relationship Between IL-18 (− 607 C/A), IL-18 (− 137 G/C), and MMP-2 (− 1306 C/T) Gene Variations and Serum Copper and Zinc Levels in Patients Diagnosed with Chronic Renal Failure

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Abstract

The aim of this study is to investigate the relationship between IL-18 (− 607 C/A), IL-18 (− 137 G/C), and MMP-2 (− 1306 C/T) gene variations and serum trace element levels in patients diagnosed with CRF. Genotype distributions of IL-18 (− 607 C/A, − 137 G/C) gene variations were determined by polymerase chain reaction (PCR) method. PCR-restriction fragment length polymorphism (RFLP) methods were used to determine the MMP-2 (− 1306 C/T) gene variation genotype distributions. Serum trace element levels were determined by atomic absorption spectrophotometer method. A significant difference was found between the CRF patient and healthy control groups in terms of genotype distributions of IL-18 (− 607 C/A) and MMP-2 (− 1306 C/T) gene variations (p < 0.05). The significant difference was found between the patient and control groups in terms of serum copper and zinc levels and copper/zinc ratio (p < 0.05). The significant difference was detected between patient and control groups in terms of copper and zinc levels and copper/zinc ratio according to IL-18 (− 607 C/A), IL-18 (− 137 G/C), and MMP-2 (− 1306 C/T) gene variations and genotype distributions (p < 0.05). In addition, significant difference was determined in terms of serum copper and zinc levels and copper/zinc ratio according to haplotypes of IL-18 (− 607 C/A), IL-18 (− 137 G/C), and MMP-2 (− 1306 C/T) gene variations between patient and control groups (p < 0.05). In conclusion, evaluation of IL-18 (− 607 C/A, − 137 G/C) and MMP-2 (− 1306 C/T) gene variations and serum trace element levels together is extremely important in terms of obtaining important biomarkers in CRF early diagnosis and progression.

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References

  1. Kazi TG, Jalbani N, Kazi N, Jamali MK, Arain MB, Afridi HI, Kandhro A et al (2008) Evaluation of toxic metals in blood and urine samples of chronic renal failure patients, before and after dialysis. Ren Fail 30(7):737–745. https://doi.org/10.1080/08860220802212999

    Article  CAS  PubMed  Google Scholar 

  2. Zima T, Tesar V, Mestek O, Nĕmecek K (1999) Trace elements in end-stage renal disease. Blood Purif 17:187–198. https://doi.org/10.1159/000014395

    Article  CAS  PubMed  Google Scholar 

  3. Zima T, Mestek O, Nĕmecek K, Bártová V, Fialová J, Tesar V, Suchánek M (1998) Trace elements in hemodialysis and continuous ambulatory peritoneal dialysis patients. Blood Purif 16(5):253–260. https://doi.org/10.1159/000014342

    Article  CAS  PubMed  Google Scholar 

  4. D’Haese PC, De Broe ME (1996) Adequacy of dialysis: trace elemens in dialysis fluids. Nephrol Dial Transplant 11(2):92–97. https://doi.org/10.1093/ndt/11.supp2.92

    Article  PubMed  Google Scholar 

  5. Lin TH, Chen JG, Liaw JM, Juang JG (1996) Trace elements and lipid peroxdation in uremic patients on hemodialysis. Biol Trace Elem Res 51(3):277–283. https://doi.org/10.1007/BF02784082

    Article  CAS  PubMed  Google Scholar 

  6. Parmar JA, Joshi AG, Raghavani PH, Raval RK, Sendhav SS, Chakrabarti M (2015) Evaluation of serum trace elements levels in patients with chronic kidney disease. Int J Res Med 4(1):93–97

    CAS  Google Scholar 

  7. Provenzano M, Andreucci M, Garofalo C, Faga T, Michael A, Ielapi N, Grande R et al (2020) The association of matrix metalloproteinases with chronic kidney disease and peripheral vascular disease: a light at the end of the tunnel? Biomolecules 10(1):154. https://doi.org/10.3390/biom10010154

    Article  CAS  PubMed Central  Google Scholar 

  8. Corredor Z, da Silva Filho MI, Rodríguez-Ribera L, Velázquez A, Hernández A, Catalano C, Hemminki K et al (2020) Genetic variants associated with chronic kidney disease in a Spanish population. Sci Rep 10:144. https://doi.org/10.1038/s41598-019-56695-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hwang E (2020) Polymorphisms in the 5’-UTR region of IL-10RA gene are associated with chronic kidney disease. Eur J Inflamm 18:1–11. https://doi.org/10.1177/2058739220959911

    Article  CAS  Google Scholar 

  10. Wang S, Dong J, Huang L (2021) Cytokine polymorphisms and predisposition to diabetic nephropathy: a meta-Analysis. Int Arch Allergy Immunol 182(2):158–165. https://doi.org/10.1159/000510250

    Article  CAS  PubMed  Google Scholar 

  11. Sakharkar P, Deb S, Mashayekhi N (2020) Association between polymorphisms in cytokine gene and viral infections in renal and liver transplant recipients: a systematic review. J Pharm Pharm Sci 23(1):109–131. https://doi.org/10.18433/jpps30961

    Article  CAS  PubMed  Google Scholar 

  12. Mai M, Jiang Y, Wu X, Liu G, Zhu Y, Zhu W (2020) Association of TGF-b1, IL-4, and IL-10 polymorphisms with chronic kidney disease susceptibility: a meta-analysis. Front Genet 11:79. https://doi.org/10.3389/fgene.2020.00079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. He J, Xie G, Wu H, Xu S, Xie J, Chen Y, Zhao X (2018) Association between inflammatory-response gene polymorphisms and risk of acute kidney injury in children. Biosci Rep 38(6):BSR20180537. https://doi.org/10.1042/BSR20180537

    Article  PubMed  PubMed Central  Google Scholar 

  14. Tsai PY, Ka SM, Chang JM, Chen HC, Shui HA, Li CY, Hua KF et al (2011) Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation. Free Radic Biol Med 51(3):744–754. https://doi.org/10.1016/j.freeradbiomed.2011.05.016

    Article  CAS  PubMed  Google Scholar 

  15. Kolesar L, Novota P, Krasna E, Slavcev A, Viklicky O, Honsova E, Striz I (2007) Polymorphism of interleukin-18 promoter influences the onset of kidney graft function after transplantation. Tissue Antigens 70(5):363–368. https://doi.org/10.1111/j.1399-0039.2007.00913.x

    Article  CAS  PubMed  Google Scholar 

  16. Chang W-S, Shen T-C, Yeh W-L, Yu C-C, Lin H-Y, Wu H-C, Tsai C-W et al (2019) Contribution of inflammatory cytokine interleukin-18 genotypes to renal cell carcinoma. Int J Mol Sci 20(7):1563. https://doi.org/10.3390/ijms20071563

    Article  CAS  PubMed Central  Google Scholar 

  17. Alkanli N, Ay A, Kehaya S, Sut N (2020) Investigation of the relationship between IL-18 (-607 C/A), IL-18 (-137 G/C) Gene variations and ischemic stroke disease development in Thrace region of Turkey. Immunol Invest 23:1–12. https://doi.org/10.1080/08820139.2020.1782932

    Article  CAS  Google Scholar 

  18. Jiang H, Cao F, Cao H, Rao Q, Yang Y (2018) Associations of human leukocyte antigen and interleukin-18 gene polymorphisms with viral load in patients with hepatitis B infection. Medicine (Baltimore) 97(30):e11249. https://doi.org/10.1097/MD.0000000000011249

    Article  CAS  Google Scholar 

  19. Davran F, Yilmaz VT, Karatoy Erdem B, Gultekin M, Suleymanlar G, Akbas H (2016) Association of interleukin 18–607A/C and -137C/G polymorphisms with oxidative stress in renal transplant recipients. Ren Fail 38(5):717–722. https://doi.org/10.3109/0886022X.2016.1158034

    Article  CAS  PubMed  Google Scholar 

  20. Catania JM, Chen G, Parrish AR (2007) Role of matrix metalloproteinases in renal pathophysiologies. Am J Physiol Renal Physiol 292(3):F905–F911. https://doi.org/10.1152/ajprenal.00421.2006

    Article  CAS  PubMed  Google Scholar 

  21. Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8(3):221–233. https://doi.org/10.1038/nrm2125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chung AW, Yang HH, Kim JM, Sigrist MK, Chum E, Gourlay WA, Levin A (2009) Upregulation of matrix metalloproteinase-2 in the arterial vasculature contributes to stiffening and vasomotor dysfunction in patients with chronic kidney disease. Circulation 120(9):792–801. https://doi.org/10.1161/circulationaha.109.862565

    Article  CAS  PubMed  Google Scholar 

  23. Yu C, Zhou Y, Miao X, Xiong P, Tan W, Lin D (2004) Functional haplotypes in the promoter of matrix metalloproteinase-2 predict risk of the occurrence and metastasis of esophageal cancer. Cancer Res 64(20):7622–7628. https://doi.org/10.1158/0008-5472.CAN-04-1521

    Article  CAS  PubMed  Google Scholar 

  24. Price SJ, Greaves DR, Watkins H (2001) Identification of novel, functional genetic variants in the human matrix metalloproteinase-2 gene: role of Sp1 in allele-specific transcriptional regulation. J Biol Chem 276(10):7549–7558. https://doi.org/10.1074/jbc.M010242200

    Article  CAS  PubMed  Google Scholar 

  25. Lee SH, Huang JW, Hung KY, Leu LJ, Kan Y (2000) Trace metals abnormalities in hemodialysis patients relationship with medication. Artif Organs 24:841–844

    Article  CAS  PubMed  Google Scholar 

  26. Seymen P, Seymen HO, Özdemir A, Belce A, Gümüştaş K, Türkmen F, Özel Barut Y (2000) Effects of cuprophan and polysulfone dialysers on oxidant/antioxidant status. Cerrahpasa J Med 31(2):74–81

    Google Scholar 

  27. Enders HM (2002) Evaluating iron status in hemodialysis patients. Nephrol Nurs J 29(4):366–370

    PubMed  Google Scholar 

  28. Vanholder R, Cornelis R, Dhondt A, Lameire N (2002) The role of trace elements in uraemic toxicity. Nephrol Dial Transplant 17(2):2–8. https://doi.org/10.1093/ndt/17.suppl_2.2

    Article  CAS  PubMed  Google Scholar 

  29. Sivrikaya A, Aköz M, Altıntepe L (2010) The serum levels of Zn, Cu, Fe, Cd, TT3, TT4, PTH and tibcin chronic renal failure patients and healthy control subjects. Van Med J 17(2):36–41

    Google Scholar 

  30. Joyce T, Rasmussen P, Melhem N, Clothier J, Booth C, Sinha MD (2020) Pediatr Nephrol 35(8):1463–1470. https://doi.org/10.1007/s00467-020-04536-0

    Article  PubMed  PubMed Central  Google Scholar 

  31. Wilk A, Szypulska-Koziarska D, Marchelek-Myśliwiec M, Głazek W, Wiszniewska B (2020) Serum selenium, iron, zinc, and copper concentrations in renal transplant recipients treated with mycophenolate mofetil. Biol Trace Elem Res 198(2):371–379. https://doi.org/10.1007/s12011-020-02074-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Toida T, Toida R, Ebihara S, Takahashi R, Komatsu H, Uezono S, Sato Y et al (2020) Association between serum zinc levels and clinical index or the body composition in incident hemodialysis patients. Nutrients 12(10):3187. https://doi.org/10.3390/nu12103187

    Article  CAS  PubMed Central  Google Scholar 

  33. Kadhim MM, Mohamed HN (2020) The significant impact of +105 A>C promoter polymorphism in IL-18 cytokine in patients with a kidney stone in Iraqi Populations. IJPR 12(2). https://doi.org/10.31838/ijpr/2020.SP2.558

  34. do Nascimento WG, Cilião DA, Genre J, Gondim DD, Alves RG, Hassan ND, Lima FP et al (2014) Genetic polymorphisms of interleukin-18 are not associated with allograft function in kidney transplant recipients. Genet Mol Biol 37(2):343–9. https://doi.org/10.1590/s1415-47572014005000005

    Article  PubMed  PubMed Central  Google Scholar 

  35. Amdur RL, Feldman HI, Gupta J, Yang W, Kanetsky P, Shlipak M, Rahman M et al (2016) CRIC Study Investigators. Inflammation and progression of CKD: the CRIC Study. Clin J Am Soc Nephrol 11(9):1546–1556. https://doi.org/10.2215/CJN.13121215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Okada R, Wakai K, Naito M, Morita E, Kawai S, Hamajima N, Hara M et al (2012) Japan Multi-Institutional Collaborative Cohort (J-MICC) Study Group. Pro-/anti-inflammatory cytokine gene polymorphisms and chronic kidney disease: a cross-sectional study. BMC Nephrol 13:2. https://doi.org/10.1186/1471-2369-13-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Piancatelli D, Maccarone D, Colanardi A, Sebastiani P, Clemente K, Iesari S, Di Pietro V et al (2016) Kidney transplantation, polymorphisms of IL-18, and other pro-inflammatory genes and late post-transplant outcome. Transplant Proc 48(2):323–325. https://doi.org/10.1016/j.transproceed.2016.02.010

    Article  CAS  PubMed  Google Scholar 

  38. Zhang PA, Wu JM, Li Y, Yang XS (2005) Association of polymorphisms of interleukin-18 gene promoter region with chronic hepatitis B in Chinese Han population. World J Gastroenterol 11(11):1594–1598. https://doi.org/10.3748/wjg.v11.i11.1594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tan RJ, Liu Y (2012) Matrix metalloproteinases in kidney homeostasis and diseases. Am J Physiol Renal Physiol 302(11):F1351–F1361. https://doi.org/10.1152/ajprenal.00037.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Marson BP, Lacchini R, Belo V, Dickel S, da Costa BP, Poli de Figueiredo CE, Tanus-Santos JE (2012) Matrix metalloproteinase (MMP)-2 genetic variants modify the circulating MMP-2 levels in end-stage kidney disease. Am J Nephrol 35(3):209–215. https://doi.org/10.1159/000336108

    Article  CAS  PubMed  Google Scholar 

  41. Cheng Z, Limbu MH, Wang Z, Liu J, Liu L, Zhang X, Chen P et al (2017) MMP-2 and 9 in Chronic Kidney Disease. Int J Mol Sci 18(4):776. https://doi.org/10.3390/ijms18040776

    Article  CAS  PubMed Central  Google Scholar 

  42. Rakhshanizadeh F, Esmaeeli M (2014) Serum zinc, copper, selenium, and lead levels in children with chronic renal failure. Rev Clin Med 1(1):21–24

    Google Scholar 

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Acknowledgements

This study was performed in the Department in Biophysics of Trakya University Medical Faculty and Department of Nephrology in Research and Application Center of Trakya University.

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Authors and Affiliations

  1. Department of Biophysics, Faculty of Medicine, Trakya University, Edirne, Turkey

    Arzu Ay

  2. Department of Biophysics, Faculty of Medicine, Haliç University, Istanbul, Turkey

    Nevra Alkanli

  3. Department of Nephrology, Faculty of Medicine, Trakya University, Edirne, Turkey

    Sedat Ustundag

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  1. Arzu Ay
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  2. Nevra Alkanli
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  3. Sedat Ustundag
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Arzu Ay, Nevra Alkanli, and Sedat Ustundag. The first draft of the manuscript was written by Arzu Ay and Nevra Alkanli, and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript. The corresponding author attests that all listed authors meet the authorship criteria and that no other authors meeting the criteria have been omitted.

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Correspondence to Arzu Ay or Nevra Alkanli.

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For our study, ethics committee approval was obtained with the TÜTF-BAEK 2019/220 protocol code from Trakya University Faculty of Medicine Non-Invasive Clinical Research Ethics Committee.

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Signed informed consent form was collected from each individual in the patient group with CRF and healthy control group.

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Ay, A., Alkanli, N. & Ustundag, S. Investigation of the Relationship Between IL-18 (− 607 C/A), IL-18 (− 137 G/C), and MMP-2 (− 1306 C/T) Gene Variations and Serum Copper and Zinc Levels in Patients Diagnosed with Chronic Renal Failure. Biol Trace Elem Res 200, 2040–2052 (2022). https://doi.org/10.1007/s12011-021-02828-6

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