Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose: proposal for a new dosing regimen

Din, Mouchira Salah El; Amin, Dalia Gamil; Ragab, Salwa B.; Ashour, Esmat; Mohamed, M. H.; Mohamed, Ahmad Magdy

doi:10.1111/j.1751-553x.2012.01426.x

Cited by 22 publications

(20 citation statements)

References 32 publications

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“…This variability in dose requirement could be attributed to the fact that CYP2C9*1 metabolizes warfarin normally, CYP2C9*2 reduces warfarin metabolism by 66%, and CYP2C9*3 reduces warfarin metabolism by 95%. These data are in agreement with those reported by previous studies conducted in Egyptian population [17,18,20].…”

Section: Discussionsupporting

confidence: 93%

“…This variability in dose requirement could be attributed to the fact that carriers of the A allele haplotype (i.e., -1639 A) produce less VKORC1 than carriers of B allele haplotype (i.e., -1639 G) [19]. These data are in agreement with those reported by previous studies conducted in Egyptian population [17,18,20].…”

Section: Discussionsupporting

confidence: 90%

“…We demonstrated that the genotype and allele frequencies of VKORC1 and CYP2C9 genetic polymorphisms were comparable with those reported by previous studies conducted in the Egyptian population [16][17][18].…”

Section: Discussionsupporting

confidence: 89%

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Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

et al. 2018

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Background/Aims: Data from previous reports, addressing the significance of genotype-guided dosing of warfarin in Egyptian patients, are infrequent and controversial. This study is aimed at demonstrating the validity of genetic dosing algorithms in Egyptian patients on warfarin therapy. Methods: A total of 100 Egyptian patients on a stable maintenance daily dose of warfarin were enrolled. The predicted warfarin dose for each patient was calculated using the warfarin dosing table, the Gage and the International Warfarin Pharmacogenetics Consortium (IWPC) clinical algorithms and the Gage and the IWPC genetic algorithms and compared to the actual dose. The accuracy of warfarin dosing algorithms was assessed by using the linear regression analysis. Results: The most accurate model in predicting the ideal dose was the Gage genetic algorithm by R² of 50.4% and the IWPC genetic algorithm by R² of 42.3%, followed by the warfarin dosing table by R² of 19.1%, and the Gage clinical algorithm by R² of 18.9% and the least accurate was the IWPC clinical algorithm by R² of 9.4%. Conclusions: The Gage genetic warfarin dosing algorithm is the best model that could be implemented in Egyptian patients starting warfarin therapy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

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Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

et al. 2018

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“…They reported that it might be possible that this was because of the minimal variation in height, which varied in the population by less than 4 %. Furthermore, El Din et al [27] reported that bodyweight showed no influence on dose variability. Moreover, the target INR in our study was 2-3.…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, there were no warfarin pharmacogenomic studies carried in Egypt, with the exception of only three studies [26,27,30] in the preceding 2 years. The novel attribute of our study was the development of a warfarin dosing algorithm based on the genetic and nongenetic factors of the study cohort, and the validation of the calculated warfarin dosing algorithm in a different cohort with a significant positive correlation observed between the predicted warfarin dose and the actual prescribed dose.…”

Section: Discussionmentioning

confidence: 99%

Validation of a Proposed Warfarin Dosing Algorithm Based on the Genetic Make-Up of Egyptian Patients

et al. 2013

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VKORC1 (1173C>T) contributes to the warfarin dose variability. Patients' age and genetic variants of VKORC1 account for nearly 20.5% of the variability in warfarin dose required to achieve an INR of 2-3. The success of a prediction equation based on these variables was proved in a different cohort: the predicted dose correlated significantly with the maintenance dose and the equation was more successful among patients with a dose≥35 mg/week. The results of the warfarin algorithm we developed were comparable with those of the IWPC and Gage algorithms with the advantage of using one SNP (VKORC1 1173C>T) only. This represents an economic advantage in our community. Replication of this study in a larger cohort of patients is necessary before translation of this knowledge into clinical guidelines for warfarin prescription.

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Cardiovascular Disease Pharmacogenomics

Chatterjee

2013

Omics for Personalized Medicine

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Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose: proposal for a new dosing regimen

Abstract: VKORC1-TT and CYP2C9 1/1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT genotype required a lower warfarin dose.

Cited by 22 publications

References 32 publications

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

Validation of a Proposed Warfarin Dosing Algorithm Based on the Genetic Make-Up of Egyptian Patients

Cardiovascular Disease Pharmacogenomics

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Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose: proposal for a new dosing regimen

Abstract: VKORC1-TT and CYP2C9 *1/*1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT genotype required a lower warfarin dose.

Cited by 22 publications

References 32 publications

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

Validation of a Proposed Warfarin Dosing Algorithm Based on the Genetic Make-Up of Egyptian Patients

Cardiovascular Disease Pharmacogenomics

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Product

Resources

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Abstract: VKORC1-TT and CYP2C9 1/1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT genotype required a lower warfarin dose.