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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients
Journal of Clinical Pharmacy and Therapeutics, Volume 37, No. 5, Year 2012
Notification
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Description
What is known and Objective: Coumarin derivatives such as acenocoumarol represent the therapy of choice for the long-term treatment and prevention of thromboembolic diseases. Many genetic, clinical and demographic factors have been shown to influence the anticoagulant dosage. Our aim was to investigate the contribution of genetic and non-genetic factors to variability in response to acenocoumarol in Moroccan patients. Methods: Our study included 114 adult Moroccan patients, receiving long-term acenocoumarol therapy for various indications. Tests for VKORC1 -1639G>A promoter polymorphism (rs9923231), CYP2C92 rs1799853, CYP2C93 rs1057910, and CYP4F2 rs2108622 alleles were undertaken using Taq Man® Pre-Developed Assay Reagents for allelic discrimination. The statistical analysis was performed using the SAS V9 statistical package. Results and Discussion: Genotyping showed that the allele frequencies for the SNPs studied were no different to those found in Caucasians population. A significant association was observed between the weekly maintenance dose and the VKORC1 (P = 0.0027) and CYP2C9 variant genotypes (P = 0.0082). A final multivariate regression model that included the target International Normalized Ratio, VKORC1 and CYP2C9 genotypes explained 36.2% of the overall interindividual variability in acenocoumarol dose requirement. What is new and Conclusion: Our study shows large interindividual variability in acenocoumarol maintenance dose requirement in our population. VKORC1 and CYP2C9 variants significantly affected acenocoumarol dose, in-line with results in other populations. For the Moroccan population, the SNPs that have the largest effect on acecoumarol dose are CYP2C9 rs1799853, CYP2C9 rs1057910 and VKORC1 rs9923231. © 2012 Blackwell Publishing Ltd.
Authors & Co-Authors
Smires, F. Z.
Morocco, Agdal Rabat
Medical School
Moreau, C.
France, Paris
Université Paris Cité
France, Paris
Hôpital Européen Georges-pompidou
Habbal, Rachida
Morocco, Casablanca
Centre Hospitalier Universitaire Ibn Rochd
Siguret, Virginie
France, Paris
Hôpital Européen Georges-pompidou
France, Paris
Université Paris Cité
Fadili, S.
Morocco, Casablanca
Centre Hospitalier Universitaire Ibn Rochd
Golmard, Jean Louis
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Assaidi, Anass
Morocco, Casablanca
Centre Hospitalier Universitaire Ibn Rochd
Beaune, Philippe
France, Paris
Université Paris Cité
France, Paris
Hôpital Européen Georges-pompidou
Loriot, Marie Anne
France, Paris
Université Paris Cité
France, Paris
Hôpital Européen Georges-pompidou
Sellama, Nadifi
Morocco, Agdal Rabat
Medical School
Statistics
Citations: 14
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.1111/j.1365-2710.2012.01340.x
ISSN:
02694727
Research Areas
Genetics And Genomics
Study Design
Cross Sectional Study
Study Approach
Quantitative