Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: role of gene polymorphism

Bazan, Naglaa Samir; Sabry, Nirmeen A.; Rizk, Amal; Mokhtar, S; Badary, Osama A.

doi:10.1007/s11845-013-0978-y

Cited by 25 publications

(34 citation statements)

References 66 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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“…However administering drug adjustment based on genotype was not suited for some patients. For example, CYP2C9*2 and CYP2C9*3 genotypes only explained 5-20% of the overall variability in warfarin dose used in previous studies (Bazan et al, 2014;Perera et al, 2013). Moreover, the results about effects of gene polymorphisms in vitro were not completely consistent with in vivo effects because the pharmacokinetics of drug might not directly reflect the metabolic activity of CYP.…”

Section: Introductionmentioning

confidence: 87%

Gene polymorphisms and contents of cytochrome P450s have only limited effects on metabolic activities in human liver microsomes

Gao

Tian

Fang

et al. 2016

European Journal of Pharmaceutical Sciences

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“…However, the extent of correlation between CYP2C9 genotype and phenotype varies between populations mainly due to the contribution of sociodemographic, epigenetic, or environmental factors, such as diet. Numerous factors affecting CYP2C9 enzyme activity have been described, including genotype, gender, age, cigarette smoking, oral contraceptives, and food constituents (Bazan et al, 2014;Giri et al, 2014;Hidaka et al, 2008;Sandberg et al, 2004). These factors might be important to consider for dose modifications (Bazan et al, 2014;Lee et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Differences inCYP2C9Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex

Hatta

Lundblad

Ramsjö

et al. 2015

OMICS: A Journal of Integrative Biology

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Global personalized medicine demands the characterization of person-to-person and between-population differences in drug pharmacokinetics and pharmacodynamics. CYP2C9 pharmacokinetic pathway is subject to modulation by both genetic and environmental factors. CYP2C9 genotype-based dose recommendations (e.g., for warfarin) is advocated. However, the overall contribution of genotype for variation in enzyme activity may differ between populations. We evaluated the importance of ethnicity, genotype, smoking, body weight, age, and sex for CYP2C9 enzyme activity. CYP2C9 genotype and phenotype was determined in 148 Swedes and 146 Koreans using losartan as a probe. CYP2C9 enzyme activity was assessed using urinary losartan/metabolite E-3174 ratio. The frequency of CYP2C9 defective variant alleles (*2 and *3) was significantly higher in Swedes (10.8% and 12.5%) than in Koreans (0% and 5.8%). In matched genotypes, CYP2C9 enzyme activity was significantly lower in Swedes compared to Koreans (p<0.0001). In a univariate analysis, age, weight, ethnicity, genotype, and smoking were significant predictors of CYP2C9 phenotype. A stepwise multivariate analysis indicated ethnicity, genotype, and smoking remained as significant predictors of CYP2C9 enzyme activity, accounting for 50% of the total variance. In both study populations, CYP2C9 genotype was a significant predictor of CYP2C9 enzyme activity, but its contribution in explaining the total variance was lower in Koreans (26.6%) than Swedes (40%). In conclusion, we report significantly lower CYP2C9 enzyme activity in Swedes compared to Koreans, partly but not exclusively due to CYP2C9 pharmacogenetic variations. Ethnicity and environment factors need to be considered together with genotype for population-specific dose optimization and global personalized medicine.

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Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: role of gene polymorphism

Abstract: VKORC1-1639G>A and CYP2C9 polymorphisms contribute to the difference in warfarin dose requirements and quality of anticoagulation amongst Egyptian patients. Study results support using personalized warfarin treatment in Egyptian patients.

Cited by 25 publications

References 66 publications

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

Gene polymorphisms and contents of cytochrome P450s have only limited effects on metabolic activities in human liver microsomes

Differences inCYP2C9Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex

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