{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T04:17:15Z","timestamp":1777868235461,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:00:00Z","timestamp":1760745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: Warfarin is a commonly used anticoagulant with a narrow therapeutic index that requires a precise dose to achieve efficacy and safety. Genetic variations in the CYP2C9 and VKORC1 genes significantly contribute to individual responses to warfarin, influencing both drug metabolism and pharmacodynamics. The current study aims to investigate the frequency of CYP2C9 and VKORC1 variant genotypes and determine the appropriate warfarin dosage for patients in Saudi Arabia. Materials and Methods: Blood samples were collected from 100 Saudi patients undergoing treatment with warfarin. DNA was extracted and purified from the whole blood, and variants in the CYP2C9 and VKORC1 genes were analyzed using multiplex PCR techniques. Results: The analysis revealed that the VKORC1 GG genotype was the most common, at 54%, followed by GA at 30%, and the AA at 16%. For CYP2C9, the *1\/*1 genotype predominated at 71%, whereas the *1\/*2 genotype was found in 14%, the *1\/*3 genotype was found in 11%, and the *2\/*3 genotype was found in in 2%, being less frequently observed. Patients with VKORC1 GG required significantly higher warfarin doses than those with GA and AA genotypes. Similarly, CYP2C9 *1\/*1 patients required higher doses than those with *1\/*3 and *2\/*3 variants. No significant differences in INR levels across genotypes were found, indicating that while genetic variations influence dosing, they do not significantly alter the therapeutic INR range. Conclusions: The findings indicate that genetic variations influence drug metabolism and response in the Saudi population, aligned with global studies. Such tailored approaches could enhance treatment efficacy and reduce adverse effects, underscoring the role of pharmacogenomics in patient care and optimizing warfarin therapy in unique genetic populations.<\/jats:p>","DOI":"10.3390\/medicina61101872","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T09:23:34Z","timestamp":1760952214000},"page":"1872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Genetic Polymorphisms of CYP2C9 and VKORC1 in the Saudi Population and Their Impact on Anticoagulant Management"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3673-9467","authenticated-orcid":false,"given":"Mohammad","family":"Al Hamad","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1016\/j.ihj.2018.02.005","article-title":"Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit","volume":"70","author":"Biswas","year":"2018","journal-title":"Indian Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1378\/chest.127.5.1515","article-title":"Effect of a centralized clinical pharmacy anticoagulation service on the outcomes of anticoagulation therapy","volume":"127","author":"Witt","year":"2005","journal-title":"Chest"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1001\/archinte.165.10.1095","article-title":"Systematic overview of warfarin and its drug and food interactions","volume":"165","author":"Holbrook","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1097\/FPC.0000000000000244","article-title":"Genetic determinants of variability in warfarin response after the dose-titration phase","volume":"26","author":"Iwuchukwu","year":"2016","journal-title":"Pharmacogenet Genom."},{"key":"ref_5","first-page":"1586","article-title":"Identification of prognostic biomarkers for patients with hepatocellular carcinoma after hepatectomy","volume":"41","author":"Wang","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1182\/blood-2005-03-1108","article-title":"The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: Proposal for a new dosing regimen","volume":"106","author":"Sconce","year":"2005","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/sj.tpj.6500313","article-title":"Common VKORC1 and GGCX polymorphisms associated with warfarin dose","volume":"5","author":"Wadelius","year":"2005","journal-title":"Pharmacogenomics J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev.med.56.082103.104724","article-title":"Pharmacogenomics and individualized drug therapy","volume":"57","author":"Eichelbaum","year":"2006","journal-title":"Annu. Rev. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/labmed\/lmx072","article-title":"Pharmacogenetics-Based Warfarin Dosing in Patients With Cardiac Valve Replacement: The Effects of CYP2C9 and VKORC1 Gene Polymorphisms","volume":"49","author":"Farzamikia","year":"2017","journal-title":"Lab. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1182\/blood-2004-06-2111","article-title":"A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin","volume":"105","author":"Chetta","year":"2005","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0149-2918(07)80081-6","article-title":"Warfarin metabolism and anticoagulant effect: A prospective, observational study of the impact of CYP2C9 genetic polymorphism in the presence of drug-disease and drug-drug interactions","volume":"29","author":"Muszkat","year":"2007","journal-title":"Clin. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2217\/17410541.5.3.225","article-title":"High carrier prevalence of combinatorial CYP2C9 and VKORC1 genotypes affecting warfarin dosing","volume":"5","author":"Ruano","year":"2008","journal-title":"Pers. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2217\/17410541.4.2.157","article-title":"Influence of CYP2C9 Genotype on warfarin dose among African American and European Americans","volume":"4","author":"Limdi","year":"2007","journal-title":"Pers. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1089\/ars.2006.8.347","article-title":"Vitamin K epoxide reductase complex subunit 1 (VKORC1): The key protein of the vitamin K cycle","volume":"8","author":"Oldenburg","year":"2006","journal-title":"Antioxid. Redox Signal"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1182\/blood-2018-01-830901","article-title":"Warfarin and vitamin K epoxide reductase: A molecular accounting for observed inhibition","volume":"132","author":"Wu","year":"2018","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.thromres.2008.11.011","article-title":"Effect of VKORC1-1639 G>A polymorphism, body weight, age, and serum albumin alterations on warfarin response in Japanese patients","volume":"124","author":"Yoshizawa","year":"2009","journal-title":"Thromb. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1177\/1076029617703483","article-title":"The Impact of Gene Polymorphisms on Anticoagulation Control With Warfarin","volume":"24","author":"Jiang","year":"2018","journal-title":"Clin. Appl. Thromb. Hemost."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"781","DOI":"10.2217\/pgs.10.49","article-title":"Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups","volume":"11","author":"Scott","year":"2010","journal-title":"Pharmacogenomics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/cpt.668","article-title":"Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update","volume":"102","author":"Johnson","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1001\/jama.2017.11469","article-title":"Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial","volume":"318","author":"Gage","year":"2017","journal-title":"JAMA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s00228-012-1404-5","article-title":"CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation","volume":"69","author":"Santos","year":"2013","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Al-Eitan, L.N., Almasri, A.Y., and Khasawneh, R.H. (2018). Impact of CYP2C9 and VKORC1 Polymorphisms on Warfarin Sensitivity and Responsiveness in Jordanian Cardiovascular Patients during the Initiation Therapy. Genes, 9.","DOI":"10.3390\/genes9120578"},{"key":"ref_23","first-page":"51","article-title":"Current issues in patient adherence and persistence: Focus on anticoagulants for the treatment and prevention of thromboembolism","volume":"4","author":"Kneeland","year":"2010","journal-title":"Patient Prefer. Adherence"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1111\/bcp.14608","article-title":"Warfarin dosing algorithms: A systematic review","volume":"87","author":"Asiimwe","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2217\/17410541.5.3.279","article-title":"Healthcare impact of personalized medicine using genetic testing: An exploratory analysis for warfarin","volume":"5","author":"McWilliam","year":"2008","journal-title":"Pers. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1046\/j.1365-2125.2002.01604.x","article-title":"Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population","volume":"53","author":"Hamdy","year":"2002","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11845-013-0978-y","article-title":"Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: Role of gene polymorphism","volume":"183","author":"Bazan","year":"2014","journal-title":"Ir. J. Med. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s40291-016-0190-7","article-title":"Association of Genetic Polymorphisms in the VKORC1 and CYP2C9 Genes with Warfarin Dosage in a Group of Kuwaiti Individuals","volume":"20","author":"Alrashid","year":"2016","journal-title":"Mol. Diagn. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/jhg.2012.94","article-title":"Warfarin pharmacogenetics: Development of a dosing algorithm for Omani patients","volume":"57","author":"Pathare","year":"2012","journal-title":"J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/clpt.2011.185","article-title":"Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing","volume":"90","author":"Johnson","year":"2011","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1159\/000486889","article-title":"Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients","volume":"139","author":"Selim","year":"2018","journal-title":"Acta Haematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102865","DOI":"10.1016\/j.cpcardiol.2024.102865","article-title":"Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population","volume":"49","author":"Fahmi","year":"2024","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"FSO276","DOI":"10.4155\/fsoa-2017-0112","article-title":"Evaluation of CYP2C9- and VKORC1-based pharmacogenetic algorithm for warfarin dose in Gaza-Palestine","volume":"4","author":"Ayesh","year":"2018","journal-title":"Future Sci. OA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ygeno.2010.11.004","article-title":"A systematic genetic polymorphism analysis of the CYP2C9 gene in four different geographical Han populations in mainland China","volume":"97","author":"Xiong","year":"2011","journal-title":"Genomics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.thromres.2014.05.028","article-title":"VKORC1 and CYP2C9 genotype distribution in Asian countries","volume":"134","author":"Gaikwad","year":"2014","journal-title":"Thromb. Res."},{"key":"ref_36","unstructured":"Pratt, V.M., Scott, S.A., Pirmohamed, M., Esquivel, B., Kattman, B.L., and Malheiro, A.J. (2012). Warfarin Therapy and VKORC1 and CYP Genotype. Medical Genetics Summaries, Bethesda."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1093\/hmg\/ddi180","article-title":"A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity","volume":"14","author":"Yuan","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1111\/bcp.12884","article-title":"Absence of ethnic differences in the pharmacokinetics of moxifloxacin, simvastatin, and meloxicam among three East Asian populations and Caucasians","volume":"81","author":"Hasunuma","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11017","DOI":"10.1007\/s11033-012-2004-2","article-title":"The prevalence of VKORC1 1639 G>A and CYP2C9*2*3 genotypes in patients that requiring anticoagulant therapy in Turkish population","volume":"39","author":"Silan","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s12041-015-0581-2","article-title":"Characterization of drug-metabolizing enzymes CYP2C9, CYP2C19 polymorphisms in Tunisian, Kuwaiti and Bahraini populations","volume":"94","author":"Abdelhedi","year":"2015","journal-title":"J. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1007\/s43440-021-00256-w","article-title":"Influence of CYP2C9, VKORC1, and CYP4F2 polymorphisms on the pharmacodynamic parameters of warfarin: A cross-sectional study","volume":"73","author":"Sridharan","year":"2021","journal-title":"Pharmacol. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1515\/dmpt-2022-0108","article-title":"Association of VKORC1 and CYP2C9 single-nucleotide polymorphisms with warfarin dose adjustment in Saudi patients","volume":"37","author":"Holail","year":"2022","journal-title":"Drug Metab. Pers. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Jokhab, S., AlRasheed, M.M., Bakheet, D., AlMomen, A., AlAboud, N., and Kamali, F. (2025). The impact of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin dose requirement in Saudi patients. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1547142"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1080\/17425255.2020.1780209","article-title":"An update on CYP2C9 polymorphisms and phenytoin metabolism: Implications for adverse effects","volume":"16","author":"Chang","year":"2020","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Park, Y.A., Song, Y.B., Yee, J., Yoon, H.Y., and Gwak, H.S. (2021). Influence of CYP2C9 Genetic Polymorphisms on the Pharmacokinetics of Losartan and Its Active Metabolite E-3174: A Systematic Review and Meta-Analysis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11070617"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41397-023-00300-3","article-title":"Targeted next-generation sequencing of genes involved in Warfarin Pharmacodynamics and pharmacokinetics pathways using the Saudi Warfarin Pharmacogenetic study (SWAP)","volume":"23","author":"Ammari","year":"2023","journal-title":"Pharmacogenomics J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"106884","DOI":"10.1016\/j.ejps.2024.106884","article-title":"In vitro assessment of inhibitory effects of kinase inhibitors on CYP2C9, 3A and 1A2: Prediction of drug-drug interaction risk with warfarin and direct oral anticoagulants","volume":"203","author":"Jin","year":"2024","journal-title":"Eur. J. Pharm. Sci."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1872\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:09:41Z","timestamp":1760954981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,18]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["medicina61101872"],"URL":"https:\/\/doi.org\/10.3390\/medicina61101872","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,18]]}}}