title: Effect of different genetics variants: CYP2C9*2, CYP2C9*3 of cytochrome P-450 CYP2C9 and 1639G>A of the VKORC1 gene; On acenocoumarol requirement in Moroccan patients.
abstract: Coumarin derivatives such as acenocoumarol represent the therapy of choice for the long-term treatment and prevention of thromboembolic diseases. Many genetics determinants involved in the metabolism of acenocoumarol have been shown to influence the anticoagulant dosage. The aim of this work was to evaluate, for the first time in Maghreb, the allelic frequencies of CYP2C9*2, CYP2C9*3 and VKORC1 -1639G>A mutations, and to establish the role of this polymorphisms in modulating the acenocoumarol requirement in Moroccan patients receiving anticoagulation treatment. Three groups of patients, with low, medium, or high acenocoumarol dose requirements were studied. Genetic analyses of VKORC1 -1639G>A, CYP2C9*2, and CYP2C9*3, were performed in 114 Moroccan patients with stable acenocoumarol dose. The results showed that the allelic frequencies of the three mutations studied was varies, most of patients having CYP2C9*2 and CYP2C9*3 mutations belong to a group with low dose of acenocoumarol, with P-value of 0.0082 and the single patient with CYP2C9*3 on homozygous form belongs to the same group and carried the A allele for VKORC1 gene. In conclusion, the present study confirmed the large interindividual variability in acenocoumarol maintenance dose due to CYP2C9*2, CYP2C9*3 and VKORC1 -1639G>A polymorphisms, and demonstrated that these alleles modulates sensitivity to acenocoumarol, a finding indicating that a reduced initial loading dose of acenocoumarol should be used in carriers of this allele, also, she indicates the usefulness of predictive testing concerning these mutations when an hypocoagulability is installed and not explained by the dose of VKA.
authors.affiliation: Medical Genetic Laboratory and Molecular Pathology, Medical School, 19 rue Tarik-Bnou-ziad, BP 9154 Casablanca, Morocco. smires_fz@yahoo.fr
authors.forename: F Z
authors.initials: FZ
authors.lastname: Smires
authors.forename: R
authors.initials: R
authors.lastname: Habbal
authors.forename: C
authors.initials: C
authors.lastname: Moreau
authors.forename: A
authors.initials: A
authors.lastname: Assaidi
authors.forename: M A
authors.initials: MA
authors.lastname: Loriot
authors.forename: S
authors.initials: S
authors.lastname: Nadifi
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009018:Morocco / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D013923:Thromboembolism / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D000074:Acenocoumarol