The impact of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin dose requirement in Saudi patients
BackgroundLimited data are available on factors that affect warfarin dose requirement in Saudi patients. Saudis are among the underrepresented ethnic groups in warfarin pharmacogenetics research. The present study investigated the frequency of CYP2C9*2 and*3, CYP4F2 (G1347A) and VKORC1 –1639G>...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1547142/full |
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| author | Salha Jokhab Maha M. AlRasheed Dana Bakheet Abdulkareem AlMomen Nouf AlAboud Farhad Kamali |
| author_facet | Salha Jokhab Maha M. AlRasheed Dana Bakheet Abdulkareem AlMomen Nouf AlAboud Farhad Kamali |
| author_sort | Salha Jokhab |
| collection | DOAJ |
| description | BackgroundLimited data are available on factors that affect warfarin dose requirement in Saudi patients. Saudis are among the underrepresented ethnic groups in warfarin pharmacogenetics research. The present study investigated the frequency of CYP2C9*2 and*3, CYP4F2 (G1347A) and VKORC1 –1639G>A genotypes and their impact on warfarin dose requirement in a cohort of Saudi patients requiring anticoagulation therapy.Methods193 patients on chronic warfarin therapy and with stable anticoagulation took part in the study. Genotyping for VKORC1 1639G>A, CYP4F2 G1347A, CYP2C9*2 430C>T and CYP2C9*3 1075A>C were performed using TaqMan genotyping assays. Analysis of variance was carried out to determine the association between CYP2C9, CYP4F2, and VKORC1 genotype and warfarin dose requirement in two groups based on target INR range. Backward linear regression analysis identified genetic and clinical factors influencing doe requirements.ResultsPatients with CYP2C9 and VKORC1 polymorphisms required significantly lower warfarin doses compared to wild-type patients. Carriers of two mutant alleles required lower doses than those with one mutant allele. In contrast, CYP4F2 polymorphisms did not influence warfarin dose. Age and genetic variants in CYP2C9 and VKORC1 were negatively correlated with dose requirements, while body surface area (BSA) was positively correlated.ConclusionSaudi patients with polymorphisms in CYP2C9 and VKORC1 required lower warfarin doses than those with the wild-type allele. CYP4F2 polymorphism had no effect on warfarin dose requirement. Integrating patient clinical factors, including age and BSA, and genetic polymorphisms in CYP2C9 and VKORC1 provides the best estimation of factors contributing to warfarin dose in the Saudi patient population. |
| format | Article |
| id | doaj-art-3f4e3c24a020457699ae2e978afc2488 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-3f4e3c24a020457699ae2e978afc24882025-08-20T03:53:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15471421547142The impact of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin dose requirement in Saudi patientsSalha Jokhab0Maha M. AlRasheed1Dana Bakheet2Abdulkareem AlMomen3Nouf AlAboud4Farhad Kamali5Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDNA Extraction and Oligo Synthesis Unit, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaMedicine-Hematology, King Khalid University Hospital, King Saud University, Riyadh, Saudi ArabiaDepartment of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United KingdomBackgroundLimited data are available on factors that affect warfarin dose requirement in Saudi patients. Saudis are among the underrepresented ethnic groups in warfarin pharmacogenetics research. The present study investigated the frequency of CYP2C9*2 and*3, CYP4F2 (G1347A) and VKORC1 –1639G>A genotypes and their impact on warfarin dose requirement in a cohort of Saudi patients requiring anticoagulation therapy.Methods193 patients on chronic warfarin therapy and with stable anticoagulation took part in the study. Genotyping for VKORC1 1639G>A, CYP4F2 G1347A, CYP2C9*2 430C>T and CYP2C9*3 1075A>C were performed using TaqMan genotyping assays. Analysis of variance was carried out to determine the association between CYP2C9, CYP4F2, and VKORC1 genotype and warfarin dose requirement in two groups based on target INR range. Backward linear regression analysis identified genetic and clinical factors influencing doe requirements.ResultsPatients with CYP2C9 and VKORC1 polymorphisms required significantly lower warfarin doses compared to wild-type patients. Carriers of two mutant alleles required lower doses than those with one mutant allele. In contrast, CYP4F2 polymorphisms did not influence warfarin dose. Age and genetic variants in CYP2C9 and VKORC1 were negatively correlated with dose requirements, while body surface area (BSA) was positively correlated.ConclusionSaudi patients with polymorphisms in CYP2C9 and VKORC1 required lower warfarin doses than those with the wild-type allele. CYP4F2 polymorphism had no effect on warfarin dose requirement. Integrating patient clinical factors, including age and BSA, and genetic polymorphisms in CYP2C9 and VKORC1 provides the best estimation of factors contributing to warfarin dose in the Saudi patient population.https://www.frontiersin.org/articles/10.3389/fphar.2025.1547142/fullwarfarinCYP2C9VKORC1CYP4F2polymorphisms |
| spellingShingle | Salha Jokhab Maha M. AlRasheed Dana Bakheet Abdulkareem AlMomen Nouf AlAboud Farhad Kamali The impact of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin dose requirement in Saudi patients Frontiers in Pharmacology warfarin CYP2C9 VKORC1 CYP4F2 polymorphisms |
| title | The impact of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin dose requirement in Saudi patients |
| title_full | The impact of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin dose requirement in Saudi patients |
| title_fullStr | The impact of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin dose requirement in Saudi patients |
| title_full_unstemmed | The impact of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin dose requirement in Saudi patients |
| title_short | The impact of CYP2C9, VKORC1, and CYP4F2 polymorphisms on warfarin dose requirement in Saudi patients |
| title_sort | impact of cyp2c9 vkorc1 and cyp4f2 polymorphisms on warfarin dose requirement in saudi patients |
| topic | warfarin CYP2C9 VKORC1 CYP4F2 polymorphisms |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1547142/full |
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