Frequency of CYP2C9 and VKORC1 Gene Polymorphisms and Their Influence on Warfarin Dose in Egyptian Pediatric Patients

• Published in: Paediatric drugs Vol. 16; no. 4; pp. 337 - 341
• Main Authors: Kamal El-Din, Mennat-Allah, Farhan, Marwa Salah, El Shiha, Randa Ibrahim, El-Kaffas, Rania Mohammed Helmy, Mousa, Somaia Mohammed
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2014; Springer; Springer Nature B.V
• Subjects: Analysis; Anticoagulants - administration & dosage; Child; Child, Preschool; Children; Cytochrome P-450 CYP2C9 - genetics; Demographic aspects; Dosage and administration; Drug therapy; Female; Gene Frequency; Genetic polymorphisms; Genotype; Health aspects; Humans; Influence; Internal Medicine; Male; Medicine; Medicine & Public Health; Original Research Article; Pediatrics; Pharmacotherapy; Polymorphism, Genetic; Thromboembolism; Vitamin K Epoxide Reductases - genetics; Warfarin; Warfarin - administration & dosage; Egypt; International Normalize Ratio; Warfarin; CYP2C9 Genotype; Warfarin Dose; Target International Normalize Ratio
• ISSN: 1174-5878; 1179-2019
• DOI: 10.1007/s40272-014-0073-5

Introduction Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 ( CYP2C9 ) and vitamin K epoxide reductase complex ( VKORC1 ) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. Methods CYP2C9 ( *2 and *3 ) alleles and the VKORC1 ( C1173T and G-1639A ) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. Results The allele frequency of the studied genes was CYP2C9*2 (0.085), CYP2C9*3 (0.12), VKORC1 1173T (0.52), and VKORC1 −1639A (0.54). In univariate analysis, patients’ age, weight, and height were significantly ( p  < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose ( p  = 0.045). Conclusion Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients.