Cornous Biology | Volume 1 Issue 3 | Pages: 1-9 | Doi : 10.37446/corbio/rsa/1.3.2023.1-9
Research Article
OPEN ACCESS | Published on : 31-Dec-2023

Association of PAI-1 4G/5G polymorphism with thrombotic risk in Sudanese patients with type 2 diabetes


    Rowida Eljack Ibrahim
  • Department of Hematology and Immunohematology, Faculty of Medical Laboratory Sciences, Managil University of Science and Technology, Managil, Sudan.

  • Khalid Abdelsamea Mohamedahmed
  • Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jerash University, Jerash, Jordan. khalid.gu89@gmail.com. ; Department of Hematology and Immunology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan. khalid.gu89@gmail.com.

  • Sanaa Elfatih Hussein Ibrahim
  • Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Al Jouf University, Sakakah, Saudi Arabia.

  • Abdarahim Ali Babikir Haj Alzebar
  • Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan.

  • Rania Ali Abdella Mohamed
  • Department of Clinical Chemistry, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan.

  • Adil Mergani Babiker
  • Department of Molecular Biology, National Cancer Institute, University of Gezira, Wad Medani, Sudan.

  • Bakri Yousif Mohamed Nour
  • Department of Medical Parasitology, Faculty of Medical Laboratory Sciences, University of Gezira, Wad Medani, Sudan.

Abstract

Introduction: The symptoms of hypercoagulability and hypofibrinolysis, which are both fatal and insignificant causes of death in this population, diabetes type 2-related mortality is linked to thrombotic complications, particularly cardiovascular ones. These complications can cause excessive fibrin deposition and accumulation within vessels, as well as the onset of thrombosis. The frequency of the 4G genotypes of the 4G/5G polymorphism of the PAI-1 gene in diabetic patients from Sudan remained unknown. The purpose of this study was to ascertain the genotype frequency of the PAI-1 gene's 4G/5G polymorphism and the relationship between this allele and thrombotic complications in individuals with type 2 diabetes from Sudan.

Methods: A case-control study with 50 healthy individuals serving as the control group and 70 diabetic patients. The polymorphism 4G/5G was genotyped using ASP-PCR (allele specific PCR), and the Hardy-Weinberg rule was used to determine the allelic frequency. For the 4G allele as a risk factor of thrombosis in diabetic patients, the allelic frequencies were determined using gene counting using the SNP-STAT program, and their connection with thrombotic complications was assessed using the X2 test and the odd ratio with (confidence intervals 95% and OR ≥1).

Results: The frequency of the 4G allele was significantly associated with the risk of thrombosis in diabetic patients, one-fold higher than that of the 5G allele (P value 0.027, CI=95%, OR =1), and there was no statistically significant difference in the frequency of the 4G allele among Sudanese diabetic patients compared to the control group (P value = 0.998).

Conclusion: Patients with type 2 diabetes who contain one 4G allele are at a high risk of thrombosis. Therefore, diabetic patients should be prescribed anticoagulant medications, namely type 2, for at least the short term to prevent thrombus formation, particularly cardiovascular events.

Keywords

4G/5G polymorphism, Diabetic mellitus type 2, PAI-1 gene, mortality, Sudan

References

  • Aburto-Mejía, E., Santiago-Germán, D., Martínez-Marino, M., Galván-Plata, M. E., Almeida-Gutiérrez, E., López-Alarcón, M., ... & Isordia-Salas, I. (2017). Hypofibrinolytic state in subjects with type 2 diabetes mellitus aggravated by the metabolic syndrome before clinical manifestations of atherothrombotic disease. BioMed Research International2017(1), 6519704.

    Almakey, E. A., Makeen, A. M., Saeed, O. K., & Mohamedahmed, K. A. Association between Adiponectin and Insulin Resistance among Sudanese Males with Type 2 Diabetes Mellitus. Chinese J Med Res., 4(2),34-37.

    Alzahrani, S. H., & Ajjan, R. (2010). Coagulation and fibrinolysis in diabetes. Diabetes and Vascular Disease Research7(4), 260-273.

    Bain, B.J., Bates, I., Laffan MA. (2016). Dacie and Lewis Practical Haematology. (12th edition). Elsevier Health Sciences. ISBN: 9780702069307

    Chevilley, A., Lesept, F., Lenoir, S., Ali, C., Parcq, J., & Vivien, D. (2015). Impacts of tissue-type plasminogen activator (tPA) on neuronal survival. Frontiers in cellular neuroscience9, 415.

    De Lange, Z., Rijken, D. C., Hoekstra, T., Conradie, K. R., Jerling, J. C., & Pieters, M. (2013). In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time. PloS one8(12), e83151.

    Eriksson, P., Kallin, B., Van't Hooft, F. M., Båvenholm, P., & Hamsten, A. (1995). Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proceedings of the National Academy of Sciences92(6), 1851-1855.

    Falk, G., Almqvist, Å., Nordenhem, A., Svensson, H., & Wiman, B. (1995). Allele specific PCR for detection of a sequence polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene. Fibrinolysis9(3), 170-174.

    Festa, A., D’Agostino Jr, R., Rich, S. S., Jenny, N. S., Tracy, R. P., & Haffner, S. M. (2003). Promoter (4G/5G) plasminogen activator inhibitor-1 genotype and plasminogen activator inhibitor-1 levels in blacks, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study. Circulation107(19), 2422-2427.

    Ibrahim, R. E., Ibrahim, S. E. H., Abdalsame, K., Alzebar, A. B. H., Babiker, A. M., & Nour, B. Y. M. (2021). Evaluation of Common Coagulation Tests in Type 2 Diabetic Patients and Association with Diabetic Pre-cardiovascular Complications, Gezira State–Sudan, 2020-2021. Asian Hematology Research Journal5(4), 1-6.

    Ibrahim, R. E., Ibrahim, S. E. H., Mohamedahmed, K. A., Alzebar, A. A. B. H., Mohamed, R. A. A., Babiker, A. M., & Nour, B. Y. M. (2022). The frequency of rs1799889 in plasminogen activator inhibitor type-1 gene in sudanese type 2 diabetic patients, gezira state, sudan, 2020-2021. Open Journal of Applied Sciences12(2), 165-174.

    Kearney, K., Tomlinson, D., Smith, K., & Ajjan, R. (2017). Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk. Cardiovascular diabetology16(1), 34.

    Khalaf, F. A., Ibrahim, H. R., Bedair, H. M., Allam, M. M., Elshormilisy, A. A., Ali, S. T., & Gaber, W. M. (2019). Plasminogen activator inhibitor-1 gene polymorphism as a risk factor for vascular complications in type 2 diabetes mellitus. Egyptian Journal of Medical Human Genetics20(1), 18.

    Longstaff, C. (2018). Measuring fibrinolysis: from research to routine diagnostic assays. Journal of Thrombosis and Haemostasis16(4), 652-662.

    Mohamedahmed, K. A., & Ibrahim, R. E. (2022). The Role of 4G allele in Plasminogen Activator Inhibitor type-1 rs1799889 Gene as Biomarker to Thrombophilic Complication among Type 2 Diabetic Patients. Galen Medical Journal11, e2447-e2447.

    Nordt, T. K., Lohrmann, J., & Bode, C. (2001). Regulation of PAI-1 expression by genetic polymorphisms: impact on atherogenesis. Thrombosis research103, S1-S5.

    Parpugga, T. K., Tatarunas, V., Skipskis, V., Kupstyte, N., Zaliaduonyte-Peksiene, D., & Lesauskaite, V. (2015). The effect of PAI‐1 4G/5G polymorphism and clinical factors on coronary artery occlusion in myocardial infarction. Disease markers2015(1), 260101.

    Schneider, D. J., & Sobel, B. E. (2012). PAI-1 and diabetes: a journey from the bench to the bedside. Diabetes care35(10), 1961-1967.

    Tjärnlund-Wolf, A., Brogren, H., Lo, E. H., & Wang, X. (2012). Plasminogen activator inhibitor-1 and thrombotic cerebrovascular diseases. Stroke43(10), 2833-2839.

    Xiao, X., Wu, Z. C., & Chou, K. C. (2011). A multi-label classifier for predicting the subcellular localization of gram-negative bacterial proteins with both single and multiple sites. PloS one6(6), e20592.

    Zhao, L., & Huang, P. (2013). Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with type 2 diabetes risk. International journal of clinical and experimental medicine6(8), 632.