Association study of uncoupling protein 2-866G/A (rs659366) gene polymorphism and serum myeloperoxidase with cardiovascular disease in type 2 diabetic patients

Document Type : Original Article

Authors

1 Clinical & Chemical Pathology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt

2 Clinical & Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt

3 Internal Medicine Department, Icahn School of Medicine at Mount Sinai, NYC Health+Hospital, Queens, New York, USA

4 Chest Unit, Ahmed Maher Teaching Hospital, Cairo, Egypt

Abstract

Diabetic cardiovascular diseases are leading causes of death. In diabetic patients, oxidative stress is key event in cardiovascular disease (CVD) development. Uncoupling protein 2 (UCP2) and myeloperoxidase (MPO) were identified as molecules regulating oxidative stress effects of oxygen free radicals. This work aimed to evaluate association of UCP2-866G/A (rs659366) gene polymorphism and serum MPO with CVD among type 2 diabetic patients. The present work was conducted on 80 type 2 diabetic Egyptian patients including 40 patients with CVD compared to 40 age- and sex-matched non-CVD patients; recruited from Outpatient Clinics in Beni-suef University Hospital and Kasr Eleiny Hospital. Lipid profile was assayed. Serum MPO was analyzed using enzyme-linked immunosorbent assay. UCP2-866G/A (rs659366) gene polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism. Statistically significant increase in concentration of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) was found among CVD patients with MPO ˃ 44.3 ng/ml (P=0.01 and 0.019, respectively). Serum MPO showed significant positive correlation with TC and LDL-C (P=0.004 and 0.002, respectively). The UCP2-866 (rs659366) (GA and AA) genotype variants did not demonstrate statistically significant higher risk to develop cardiovascular events, yet were observed to have higher frequency among CVD patients and among patients with MPO ˃ 44.3ng/ml. In conclusion, our results revealed significant correlation between serum myeloperoxidase and CVD lipid risk factors in diabetic patients. This study suggests UCP2 -866G/A (rs659366) gene polymorphism and MPO as target assay studies on CVD etiology and oxidative stress parameters evaluation among type 2 diabetic patients.

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Main Subjects

References

  1. Zhang L, Yang H, & Yang P (2022). The correlation between type 2 diabetes mellitus and cardiovascular disease risk factors in the elderly. Applied Bionics and Biomechanics ; Article ID 4154426, https://doi.org/10.1155/2022/4154426
  2. Einarson TR, Ludwig C, & Panton UH (2018). Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovascular Diabetology; 17(1):1–19.
  3. Almourani R, Chinnakotla B, Patel R, Kurukulasuriya LR, & Sowers J (2019). Diabetes and cardiovascular disease: an update. Current Diabetes Reports; 19(12): 161. https://doi.org/10.1007/s11892-019-1239-x
  4. Cho NH. International Diabetes Federation.IDF Diabetes Atlas, IDF Diabetes Atlas, Brussels, Belgium, 9th edition, 2019.
  5. Senoner T & Dichtl W (2019). Oxidative stress in cardiovascular diseases: Still a therapeutic target? Nutrients;11(9):2090. doi:10.3390/nu11092090
  6. Tang Z, Wang P, Dong C, Zhang J, Wang X, & Pei H (2022). Oxidative stress signaling mediated pathogenesis of diabetic cardiomyopathy. Oxidative Medicine and Cellular Longevity; Article ID 5913374, 8 pages https://doi.org/10.1155/2022/5913374
  7. Kehrer JP & Klotz LO (2015). Free radicals and related reactive species as mediators of tissue injury and disease: implications for health. Crit Rev Toxicol; 45:765–98.
  8. Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, & Bitto A (2017). Oxidative stress: Harms and benefits for human health. Oxid Med Cell Longev; doi: 10.1155/2017/8416763
  9. Liu Q, Liu Y, Shi J, Gao M, Liu Y, Cong Y, Li Y, Wang Y, Yu M, Lu Y, Wang D, Chen S, Zheng Y, & Cheng Y (2018). Entire peroxidation reaction system of myeloperoxidase correlates with progressive low-density lipoprotein modifications via reactive aldehydes in atherosclerotic patients with hypertension.Cell Physiol Biochem;50:1245–1254
  10. Hawkins CL &  Davies MJ (2021). Role of myeloperoxidase and oxidant formation in the extracellular environment in inflammation-induced tissue damage. Free Radical Biology and Medicine; 172: 633-651.
  11. Teng N, Maghzal GJ, Talib J, Rashid I, Lau AK, & Stocker R (2017). The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture, Redox Report; 22(2):51-73. DOI: 10.1080/13510002.2016.1256119
  12. Monteiro, BS, Freire-Brito L, Carrageta DF, Oliveira PF, & Alves, MG (2021). Mitochondrial uncoupling proteins (UCPs) as key modulators of ROS homeostasis: A crosstalk between diabesity and male infertility? Antioxidants; 10: 1746. https:// doi. org/ 10.3390/ antiox 10111746
  13. Cadenas S (2018). Mitochondrial uncoupling, ROS generation and cardioprotection. Biochim. Biophys. Acta Bioenerg;1859:940e950.
  14. Gamboa  R, Gómez CH, Pérez VL, Sánchez RP, Saldaña GC, Urrutia AM, Rojas JGJ, Soto ME, Romero CP, &  Alarcón GV (2018). The UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms are associated with premature coronary artery disease and cardiovascular risk factors in Mexican population. Genetics and Molecular Biology; 41(2): 371-378.
  15. Ježek P, Holendová B, Garlid KD, & Jabůrek M (2018). Mitochondrial uncoupling proteins: subtle regulators of cellular redox signaling. Antioxid Redox Signal; 29(7) https://doi.org/10.1089/ars.2017.7225
  16. Pravednikova AE, Shevchenko SY, Kerchev VV, Skhirtladze MR, Larina SN, Kachaev ZM, Egorov AD, & Shidlovskii YV (2020). Association of uncoupling protein (Ucp) gene polymorphisms with cardiometabolic diseases. Mol Med; 26(1):51. doi: 10.1186/s10020-020-00180-4
  17. World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. The 59th WMA General Assembly, Seoul, South Korea. 2008.
  18. Oktavianthi S,  Trimarsanto H,  Febinia CA,  Suastika K,  Saraswati MR, Dwipayana P,  Arindrarto W,  Sudoyo H,  & Malik SG (2012). Uncoupling protein 2 gene polymorphisms are associated with obesity. Cardiovasc Diabetol ; 11: 41. doi: 10.1186/1475-2840-11-41
  19. Dawson B and Trapp RG. Basic and clinical biostatistics, Mcgrow-Hill Inc. Third edition. 2001.
  20. Erdem D, Gunaldi M, Isiksacan N, Karaman I, Pehlivan M, & Pehlivan S (2020). Evaluation of the relationship between antioxidant gene polymorphisms (endothelial nitric oxide synthase, myeloperoxidase, uncoupling protein 2) and breast cancer. EJMO; 4(4):265–270.
  21. El- Alameey IR, Ahmed HH, Mahmoud RA,  Kairy SA,  & Medany EA (2019). Significance of myeloperoxidase in the onset of cardiovascular disease among obese children and adolescents. Biomedical and Pharmacology Journal;12 (4):1647. DOI :  https :// dx. doi.org/10.13005/bpj/1795
  22. Kimak E, Zięba B, Duma D, & Solski J (2018). Myeloperoxidase level and inflammatory markers and lipid and lipoprotein parameters in stable coronary artery disease. Lipids Health Dis; 17(1):71. doi: 10.1186/s12944-018-0718-4
  23. Vasilyev VB, Sokolov AV, Kostevich VA, Elizarova AY, Gorbunov NP, & Panasenko OM (2021). Binding of lactoferrin to the surface of low-density lipoproteins modified by myeloperoxidase prevents intracellular cholesterol accumulation by human blood monocytes. Biochem Cell Biol;99 (1):109-116. doi: 10.1139/bcb-2020-0141
  24. Variji A, Shokri Y, Fallahpour S, Zargari M, Bagheri B, Abediankenari S, Alizadeh A, & Mahrooz A (2019). The combined utility of myeloperoxidase (MPO) and paraoxonase 1 (PON1) as two important HDL-associated enzymes in coronary artery disease: Which has a stronger predictive role? Atherosclerosis; 280:7-13. doi: 10.1016/j.atherosclerosis.2018.11.004
  25. Tian XY, Ma S, Tse G, Wong WT, & Huang Y (2018). Uncoupling protein 2 in cardiovascular health and disease. Front Physiol; 2 (9):1060. doi: 10.3389/fphys.2018.01060
  26. Lapik IA, Sharafetdinov KK, Plotnikova OA, Sorokina EY, Sentsova TB, & Baturin AK (2015). Personalized therapy in patients with type 2 diabetes based molecular genetic studies. Russ Med J; 23(29):32–4.
  27. Hou G, Jin Y, Liu M, Wang C, & Song G (2020). UCP2–866G/A Polymorphism is associated with prediabetes and type 2 diabetes. Archives of Medical Research; 51 (6), 556-563.
  28. Souza BMd, Michels M, Sortica DA, Bouças AP, Rheinheimer J, Buffon MP, Bauer AC, Canani LH, & Crispim D (2015). Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney. Plos One; 10(7): e0132938. https://doi.org/10.1371/journal.pone.0132938
  29. Quan N, Wang L, Chen X, Luckett C, Cates C, Rousselle T, Zheng Y, & Li J (2018). Sestrin2 prevents age-related intolerance to post myocardial infarction via AMPK/PGC-1α pathway. J Mol Cell Cardiol; 115:170-178. doi: 10.1016/j.yjmcc.2018.01.005
  30. Castillo RL, Herrera EA, Gonzalez-Candia A, Reyes-Farias M, de la Jara N, Peña JP, & Carrasco-Pozo C (2018). Quercetin prevents diastolic dysfunction induced by a high-cholesterol diet: role of oxidative stress and bioenergetics in hyperglycemic rats. Oxid Med Cell Longev; 2018: 7239123. doi: 10.1155/2018/7239123
  31. Wang Y, Lei T, Yuan J, Wu Y, Shen X, Gao J, Feng W, & Lu Z (2018). GCN2 deficiency ameliorates doxorubicin-induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress. Redox Biol;17:25-34. doi: 10.1016/j.redox.2018.04.009
Egyptian Journal of Medical Research
Volume 4, Issue 1
January 2023
Pages 114-129

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