ASSOCIATION OF EDN1 rs10478694 POLYMORPHISM AND SERUM LEVELS OF ET-1 WITH CARDIOVASCULAR DISEASE IN THE DUHOK POPULATION
Article Sidebar
-
Endothelin 1rs10478694 polymorphism, Coronary Artery Disease, Hypertension
Abstract
This study investigated the association of the Endothelin-1 (EDN1) rs10478694 polymorphism and serum ET-1 levels with coronary artery disease (CAD) and hypertension in the Duhok Province population. Cardiovascular diseases (CVDs) represent a significant global health burden, and understanding their genetic predispositions is critical for targeted interventions. The endothelin system, particularly ET-1, is integral in vascular tone regulation and frequently implicated in various cardiovascular conditions. We conducted a case-control study involving 202 individuals, categorized into control, CAD, hypertension, and combined CAD/hypertension groups. Genotyping for EDN1 rs10478694 was performed via PCR-RFLP, and serum ET-1 levels were quantified by ELISA. Our findings revealed statistically significant associations: the 'rr' genotype and 'r' allele exhibited higher prevalence in all patient groups compared to controls (CAD: genotype p=0.021, allele p=0.022; Hypertension: genotype p=0.022, allele p=0.015; CAD with Hypertension: genotype p=0.021, allele p=0.012). This outcome suggests an elevated genetic susceptibility associated with the 'r' allele. Furthermore, a weak positive correlation between the 'r' allele/rr genotype and serum ET-1 levels substantiated a plausible biological mechanism affecting ET-1 expression and subsequent CVD risk. These results significantly enhance our understanding of CVD genetic architecture in this distinct population, thereby facilitating improved risk stratification and personalized prevention strategies.
Full text article
References
Abbas, A. M., Jubrael, J. M. S., & Mohammed, A. B. (2023). Caprine Myostatin Gene Polymorphism in Domestic and Wild Goat Breeds in Duhok Province/Kurdistan Region of Iraq Using PCR-RFLP and SNP Markers. Science Journal of University of Zakho, 11(2), 280–285. https://doi.org/10.25271/sjuoz.2023.11.2.1045
Ahlqvist, V. H., & Ballin, M. (2023). Genetic and Environmental Factors and Cardiovascular Disease Risk in Adolescents. JAMA Network Open, 6(11), e2343947. https://doi.org/10.1001/jamanetworkopen.2023.43947
Barton, M., & Ruschitzka, F. (2011). Endothelin and endothelin antagonism in cardiovascular disease: A brief update. Journal of Hypertension, 29(2), 209–218. https://doi.org/10.1097/HJH.0b013e32834164c9
Brvar, M., Zupan, N., Trkov, A., & Mlinaric, M. (2022). Endothelin-1 gene polymorphism rs10478694 is associated with vasovagal syncope. Clinical Autonomic Research, 32(1), 59–66. https://doi.org/10.1007/s10286-021-00854-4
Cheng, M., Zhang, M., Zhang, B., Dong, G., Wang, M., Wu, M., & Yang, B. (2021). The rs10478694 polymorphism in the Endothelin-1 gene is associated with hypertension: A meta-analysis. Journal of Clinical Hypertension, 23(8), 1540–1549. https://doi.org/10.1111/jch.14232
CLSI. (2024). Handling, transport, processing, and storage of blood specimens for routine laboratory examinations (PRE04 Ed1). Clinical and Laboratory Standards Institute.
Ebrahimi, N., Asadikaram, G., Mohammadi, A., Jahani, Y., Moridi, M., & Masoumi, M. (2019). The association of endothelin-1 gene polymorphism and its plasma levels with hypertension and coronary atherosclerosis. Archives of Medical Science, 17(3), 613–620. https://doi.org/10.5114/aoms.2019.86532
Ford, T. J., Corcoran, D., Padmanabhan, S., Aman, A., Rocchiccioli, P., Good, R., McEntegart, M., Maguire, J. J., Watkins, S., & Eteiba, H. (2020). Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction. European Heart Journal, 41(34), 3239–3249. https://doi.org/10.1093/eurheartj/ehaa440
Khasawneh, R. M., Al-Tarawneh, S., & Al-Tarawneh, I. (2022). Endothelin-1 gene polymorphism and its association with hypertension: A systematic review and meta-analysis. Hypertension Research, 45(2), 273–281. https://doi.org/10.1038/s41440-021-00832-7
Kim, B. J., Lee, S. H., Lee, M. Y., Lee, S. J., & Choi, H. I. (2023). Comparison of office blood pressure, automated unattended office blood pressure, home blood pressure, and 24-hour ambulatory blood pressure measurements. Journal of Korean Medical Science, 38(48), e379. https://doi.org/10.3346/jkms.2023.38.e379
Maguire, J. J., & Davenport, A. P. (2015). Endothelin and its receptors: New insights and therapeutic opportunities. Pharmacological Reviews, 67(1), 179–211. https://doi.org/10.1124/pr.114.009908
Mälarstig, A., Nordström, P., Lampa, E., Ohman, K., & Jansson, J. H. (2008). Association of endothelin-1 (EDN1) gene polymorphisms and endothelin-1 levels with risk of myocardial infarction. BMC Medical Genetics, 9(1), 10. https://doi.org/10.1186/1471-2350-9-10
Oo, W. M., & Khine, M. M. (2018). Retrospect on Endothelin-1 gene (EDN1) polymorphisms in essential
hypertension. Journal of Biological Sciences and Medicine, 4(2), 35–41.
Popowski, K., Speer, G., Schütt, B., Wurl, M., & Schulte, H. H. (2004). Functional significance of a hereditary adenine insertion variant in the 5'-UTR of the endothelin-1 gene. Journal of Molecular Medicine, 82(10), 682–688. https://doi.org/10.1007/s00109-004-0570-5
Roth, G. A., Mensah, G. A., Johnson, C. O., Addolorato, G., Baltrusaitis, J., Bigna, J. J., ... & Glenn, S. D. (2023). Global burden of cardiovascular diseases and risks, 1990–2021. Journal of the American College of Cardiology, 82(19), 1775-1811. https://doi.org/10.1016/j.jacc.2023.11.007
Thye, J., Thomsen, H. K., Møller, C. L., & Bendix, L. (2009). The endothelin-1 5'-untranslated region polymorphism and its association with essential hypertension: A meta-analysis. Journal of Human Hypertension, 23(1), 13–19. https://doi.org/10.1038/jhh.2008.106
Turovskaya, M. V., & Anfinogenova, Y. A. (2022). Endothelin-1-Induced Oxidative Stress and Inflammation in Endothelial Dysfunction. International Journal of Molecular Sciences, 23(17), 9637. https://doi.org/10.3390/ijms23179637
Williams, B., Mancia, G., Spiering, W., Agabiti Rosei, E., Azizi, M., Burnier, M., Clement, D. L., Coca, A., De Simone, G., Dominiczak, A., & Kahan, T. (2018). 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European Heart Journal, 39(33), 3021–3104. https://doi.org/10.1093/eurheartj/ehy339
World Health Organization. (2024). World health statistics 2024. https://iris.who.int/bitstream/handle/10665/376869/9789240094703-eng.pdf
Yildirim, M., Akkus, S., Bayrak, B., Yilmaz, F., Kutuk, H., & Kaynar, M. (2016). Endothelin-1 Lys198Asn and rs10478694 polymorphism in ischemic stroke. Journal of Clinical and Analytical Medicine, 7(Suppl. 1), 60–63. https://doi.org/10.4328/JOCAM.4329
Zintzaras, E., Lau, J., & Thye, J. (2010). Genetic polymorphisms of the endothelin system and essential hypertension: A systematic review and meta-analysis. Journal of Human Hypertension, 24(1), 14–23. https://doi.org/10.1038/jhh.2009.61
Authors
Copyright (c) 2026 Omer A Mohammed Ameen and Awat Mustafa Abbas
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License [CC BY-NC-SA 4.0] that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work, with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online.