Association of Cyclooxygenase 2 (COX2) Polymorphism at SNP RS20417 with Aspirin Resistance in Pakistani Patients with Ischemic Heart Disease
DOI:
https://doi.org/10.51253/pafmj.v74i3.11131Keywords:
Aspirin resistance, Cyclooxygenase 2 polymorphism, Ischemic heart disease, Platelet aggregation, Restriction fragment length (RFLP), Single nucleotide (SNP) rs20417Abstract
Objective: to find a link between a single nucleotide polymorphism (SNP) called rs20417 in the cyclooxygenase-2 gene and Aspirin resistance in Pakistani patients with heart disease.
Study Design: Cross-sectional study.
Place and Duration of Study: Pharmacology Department, National University of Medical Sciences, in collaboration with the National Institute of Heart Diseases and the Institute of Biomedical and Genetic Engineering in Islamabad Pakistan, from Oct 2018 to Dec 2021.
Methodology: The study was carried out on 384 patients (272 males and 112 females) with ischemic heart disease. Patients who had been on Aspirin for at least seven days were selected using non-probability convenience sampling. Platelet aggregation was performed using a Transmission Aggregometer, with arachidonic acid as an agonist. DNA extraction was done using the kit method (Invitrogen, Thermofisher). Then, Polymerase chain Reaction, Restriction Fragment Length Polymorphism, and gel electrophoresis were used to identify SNP rs20417.
Results: In this study, 14.0% (n=54) of ischemic heart disease patients were found to be Aspirin resistant, while 86.0% (n=330) were Aspirin responders. The genotyping of COX2 SNP rs20417 showed that 55.46% (n=213) of patients were homozygous with the GG genotype, 34.11%(n=131) had CG (heterozygous), and 10.41% (n=40) of patients were carriers of homogeneous (CC). Statistical analysis did not demonstrate a significant association of any of the alleles of the evaluated SNP with Aspirin resistance (p>0.05).
Conclusion: In the Pakistani population, Aspirin resistance is not associated with any specific polymorphic form of Cyclooxygenase-2 at SNP rs20417.
Downloads
References
Vaduganathan M, Mensah GA, Turco JV, Fuster V, Roth GA. The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health. J Am Coll Cardiol 2022; 80(25): 2361-2371. https://doi.org/10.1016/j.jacc.2022.11.005
Zubair F, Nawaz SK, Nawaz A, Nangyal H, Amjad N, Khan MS. Prevalence of cardiovascular diseases in Punjab, Pakistan: a cross-sectional study. J Public Health. 2018; 26(5): 523-529. https://doi.org/10.1007/s10389-018-0898-4
Cardillo G, Barakat AI. A computational model of chemically and mechanically induced platelet plug formation. bioRxiv 2023. https://doi.org/10.1101/2023.01.26.525741
Viet-Duc D, Thanh-Huy N, Quoc-Quy T, Tat-Tho N. Molecular Histopathology and Cytopathology in Cardiovascular Diseases. Molecular Histopathology and Cytopathology. IntechOpen; 2023. http://doi.org/10.5772/intechopen.110503
Zehnder JL. Drugs used in disorders of coagulation. Katzung BG(Ed.), Basic & Clinical Pharmacology, 14th Edition. McGraw-Hill Education; 2017.
Ebrahimi P, Farhadi Z, Behzadifar M, Shabaninejad H, Abolghasem Gorji H, Taheri-Mirghaed M, et al. Prevalence rate of laboratory defined aspirin resistance in cardiovascular disease patients: A systematic review and meta-analysis. Caspian J Intern Med 2020; 11(2): 124-134.
https://doi.org/10.22088/cjim.11.2.124
Wang L, Shao C, Han C, Li P, Wang F, Wang Y, et al. Correlation of ApoE gene polymorphism with acute myocardial infarction and aspirin resistance after percutaneous coronary intervention. Am J Transl Res 2022; 14(5): 3303-3310.
Unsworth AJ, Bye AP, Sage T, Gaspar RS, Eaton N, Drew C, et al. Antiplatelet properties of Pim kinase inhibition are mediated through disruption of thromboxane A2 receptor signaling. Haematologica 2021;106(7):1968-1978.
https://doi.org/10.3324/haematol.2019.223529
Josefsson EC, Vainchenker W, James C. Regulation of Platelet Production and Life Span: Role of Bcl-xL and Potential Implications for Human Platelet Diseases. Int J Mol Sci 2020; 21(20): 7591. https://doi.org/10.3390/ijms21207591
Zhou J, Li Y, Ji J, Chen S, Zhang J, He S. Predictive Value of Heart Rate Variability Indexes for 2-year Prognosis of the Patients after Transcatheter Aortic Valve Replacement. J Coll Physicians Surg Pak 2022; 32(7): 843-847.
https://doi.org/10.29271/jcpsp.2022.07.843
Noor M, Nawaz U, Fazal I, Waheed A. Aspirinresistance: An emerging threat to cardiovascular disease patients andits association with age and gender. Pak Heart J 2018; 51 (02):119-123.
Yi X, Cheng W, Lin J, Zhou Q, Wang C. Interaction between COX-1 and COX-2 Variants Associated with Aspirin Resistance in Chinese Stroke Patients. J Stroke Cerebrovasc Dis 2016; 25(9): 2136-2144.
https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.05.039
Gum PA, Kottke-Marchant K, Poggio ED, Gurm H, Welsh PA, Brooks L, et al. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 2001; 88(3): 230-235. https://doi.org/10.1016/s0002-9149(01)01631-9
Haghshenas M, Koosha M, Latifi A, Kazemirad E, Dehghan A, Nikmanesh B, et al. Detection of Enterobius vermicularis in archived formalin-fixed paraffin-embedded (FFPE) appendectomy blocks: It's potential to compare genetic variations based on mitochondrial DNA (cox1) gene. PLoS One 2023; 18(2): e0281622.
https://doi.org/ 10.1371/journal.pone.0281622
Lezheiko TV, Golimbet VE, Andryushchenko AV, Melik-Pashayan AE, Mironova EV. Studies of the Association between the Kynurenine-3-Monooxygenase Gene and Depression. Neurosc Behav Physiol 2018; 48(4): 416-419.
Yi X, Wang C, Zhou Q, Lin J. Interaction among COX-2, P2Y1 and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients. BMC Neurol 2017; 17(1): 4. https://doi.org/10.1186/s12883-016-0788-8
Du G, Lin Q, Wang J. A brief review on the mechanisms of aspirin resistance. Int J Cardiol 2016; 220: 21-26.
https://doi.org/10.1016/j.ijcard.2016.06.104
Weng Z, Li X, Li Y, Lin J, Peng F, Niu W. The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity: a meta-analysis. PLoS One 2013; 8(11): e78093.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Mudassar Noor, Syed Zubair Hussain Shah, Usman Nawaz, Qaiser Mansoor
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.