Impact of CYP2C9 and VKORC1 genetic polymorphisms upon warfarin dose requirements in Egyptian patients with acute coronary syndrome

Ghozlan, Manal Fawzy; Foad, Dina A.; Darwish, Yasser W.; Saad, Abeer A.

doi:10.1097/mbc.0000000000000272

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…However, the study by Alrashid et al [38] was considered of poor quality as there was no reporting of the r 2 value for the dosing model. The sample-size used in some of the studies was less than 100, which is relatively low and may have affected the power of their conclusions [31, 32, 34, 39]. Testing for the Hardy-Weinberg equilibrium was reported in all studies except those by Yildirim et al [44] and Ghozlan et al [32].…”

Section: Resultsmentioning

confidence: 99%

“…al. [32]. Such discrepancy could be in part due to the small sample sizes used in the different studies concerning the Egyptian population, in particular the studies by Ghozlan, Ekladious, and Bazan and their colleagues [31, 32, 34].…”

Section: Discussionmentioning

confidence: 99%

“…[32]. Such discrepancy could be in part due to the small sample sizes used in the different studies concerning the Egyptian population, in particular the studies by Ghozlan, Ekladious, and Bazan and their colleagues [31, 32, 34]. Moreover, the Egyptian population is a heavily admixed population with different ethnic origins [12] which may have led to different frequencies depending on the ethnicity of the studied population.…”

Section: Discussionmentioning

confidence: 99%

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The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review

Bader

Elewa

2016

PLoS ONE

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BackgroundWarfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing.ObjectiveTo explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose.MethodsIn this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews.ResultsWe identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients.ConclusionVariants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin dose.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review

Bader

Elewa

2016

PLoS ONE

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“…have demonstrated that there is a strong association between CYP2C9 variant alleles and warfarin dose requirement . After that, many studies have certified the significant effect of CYP2C9 on warfarin doses in adult patients . Moreover, a dosing algorithm for adult patients has been established by the US Food and Drug Administration and International Warfarin Pharmacogenetics Consortium .…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 2C9 gene polymorphism and warfarin maintenance dosage in pediatric patients: A systematic review and meta‐analysis

Zhang

Tian²,

et al. 2016

Cardiovascular Therapeutics

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We found that CYP2C9 gene polymorphism (referring to the presence of *1/*2, *1/*3, and variant genotypes in the population in addition to the wild type) was significantly associated with decreased warfarin maintenance dose requirements. Additionally, a specific indication for warfarin, the Fontan procedure, was associated with a lower daily warfarin dose. However, the results of our study require confirmation from more research with larger numbers of pediatric patients.

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“…The estimated regression equation was able to account for 20.5% of the overall variability in warfarin maintenance dose. Similarly, Ghozlan et al [24] reported that genetic polymorphisms in VKORC1, CYP2C9 along with age and height were determinants of warfarin dose requirements in Egyptian population with acute coronary syndrome.…”

Section: Discussionmentioning

confidence: 99%

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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Impact of CYP2C9 and VKORC1 genetic polymorphisms upon warfarin dose requirements in Egyptian patients with acute coronary syndrome

Cited by 9 publications

References 30 publications

The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review

The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review

Cytochrome P450 2C9 gene polymorphism and warfarin maintenance dosage in pediatric patients: A systematic review and meta‐analysis

Pharmacogenetic Warfarin Dosing Algorithms: Validity in Egyptian Patients

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