The impact of age and CYP2C9 and VKORC1 variants on stable warfarin dose in the paediatric population

British Journal of Haematology

Volumn 165, Issue 6, 2014, Pages 832-835

  Vear, Susan I ^a   Ayers, Gregory D ^b   Van Driest, Sara L ^a   Sidonio, Robert F ^a   Stein, Charles Michael ^b   Ho, Richard H ^a  

^a MONROE CARELL JR CHILDREN S HOSPITAL AT VANDERBILT   (United States)

^b VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

CYP2C9; Paediatrics; Pharmacogenomics; VKORC1; Warfarin

Indexed keywords

WARFARIN;

AGE; ARTICLE; CHILD; CROSS-SECTIONAL STUDY; CYP2C9 GENE; CYP4F2 GENE; DEEP VEIN THROMBOSIS; GENE; GENE FREQUENCY; GENE INTERACTION; GENETIC VARIABILITY; HOMOZYGOSITY; HUMAN; INTERNATIONAL NORMALIZED RATIO; MAJOR CLINICAL STUDY; PHARMACOGENOMICS; PRIORITY JOURNAL; PROSTHETIC VALVE THROMBOSIS; RETROSPECTIVE STUDY; SENSITIVITY ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM; TREATMENT INDICATION; VKORC1 GENE;

CYP2C9; PAEDIATRICS; PHARMACOGENOMICS; VKORC1; WARFARIN;

ADOLESCENT; AGE FACTORS; ALLELES; ANTICOAGULANTS; ARYL HYDROCARBON HYDROXYLASES; CHILD; CHILD, PRESCHOOL; CROSS-SECTIONAL STUDIES; GENETIC VARIATION; GENOTYPE; HUMANS; INFANT; PHARMACOGENETICS; RETROSPECTIVE STUDIES; VITAMIN K EPOXIDE REDUCTASES; WARFARIN;

EID: 84901690770     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.12817     Document Type: Article

References (15)

1. Biss, T.T., Avery, P.J., Brandao, L.R., Chalmers, E.A., Williams, M.D., Grainger, J.D., Leathart, J.B.S., Hanley, J.P., Daly, A.K. & Kamali, F. (2012) VKORC1 and CYP2C9 genotype and patient characteristics explain a large proportion of the variability in warfarin dose requirement among children. Blood, 119, 868-873.
2. Cresteil, T., Beaune, P., Kremers, P., Celier, C., Guengerich, F.P. & Leroux, J.P. (1985) Immunoquantification of epoxide hydrolase and cytochrome P-450 isozymes in fetal and adult human liver microsomes. European Journal of Biochemistry/FEBS, 151, 345-350.
3. Hirai, K., Hayashi, H., Ono, Y., Izumiya, K., Tanaka, M., Suzuki, T., Sakamoto, T. & Itoh, K. (2013) Influence of CYP4F2 polymorphisms and plasma vitamin K levels on warfarin sensitivity in Japanese pediatric patients. Drug Metabolism and Pharmacokinetics, 28, 132-137.
4. Johnson, J.A., Gong, L., Whirl-Carrillo, M., Gage, B.F., Scott, S.A., Stein, C.M., Anderson, J.L., Kimmel, S.E., Lee, M.-T.M., Pirmohamed, M., Wadelius, M., Klein, T.E. & Altman, R.B. (2011) Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clinical Pharmacology and Therapeutics, 90, 625-629.
5. Monagle, P., Chalmers, E., Chan, A., deVeber, G., Kirkham, F., Massicotte, P. & Michelson, A.D. (2008) Antithrombotic therapy in neonates and children: American college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest, 133, 887S-968S.
6. Moreau, C., Bajolle, F., Siguret, V., Lasne, D., Golmard, J.L., Elie, C., Beaune, P., Cheurfi, R., Bonnet, D. & Loriot, M.A. (2012) Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement. Blood, 119, 861-867.
7. Nguyen, N., Anley, P., Yu, M.Y., Zhang, G., Thompson, A.A. & Jennings, L.J. (2012) Genetic and clinical determinants influencing warfarin dosing in children with heart disease. Pediatric Cardiology, 34, 984-990.
8. Nowak-Gottl, U., Dietrich, K., Schaffranek, D., Eldin, N.S., Yasui, Y., Geisen, C. & Mitchell, L.G. (2010) In pediatric patients, age has more impact on dosing of vitamin K antagonists than VKORC1 or CYP2C9 genotypes. Blood, 116, 6101-6105.
9. Oldenburg, J., Bevans, C.G., Müller, C.R. & Watzka, M. (2006) Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle. Antioxidants & Redox Signaling, 8, 347-353.
10. Owen, R.P., Gong, L., Sagreiya, H., Klein, T.E. & Altman, R.B. (2010) VKORC1 pharmacogenomics summary. Pharmacogenetics and Genomics, 20, 642-644.
11. Rieder, M.J., Reiner, A.P., Gage, B.F., Nickerson, D.A., Eby, C.S., McLeod, H.L., Blough, D.K., Thummel, K.E., Veenstra, D.L. & Rettie, A.E. (2005) Effect of VKORC1Haplotypes on transcriptional regulation and warfarin dose. The New England Journal of Medicine, 352, 2285-2293.
12. Salem, F., Johnson, T.N., Barter, Z.E., Leeder, J.S. & Rostami Hodjegan, A. (2013) Age related changes in fractional elimination pathways for drugs: assessing the impact of variable ontogeny on metabolic drug-drug interactions. The Journal of Clinical Pharmacology, 53, 857-865.
13. Treluyer, J.M., Gueret, G., Cheron, G., Sonnier, M. & Cresteil, T. (1997) Developmental expression of CYP2C and CYP2C-dependent activities in the human liver: in-vivo/in-vitro correlation and inducibility. Pharmacogenetics, 7, 441-452.
14. Vear, S.I., Stein, C.M. & Ho, R.H. (2013) Warfarin pharmacogenomics in children. Pediatric Blood & Cancer, 60, 1402-1407.
15. Yang, L., Ge, W., Yu, F. & Zhu, H. (2010) Impact of VKORC1 gene polymorphism on interindividual and interethnic warfarin dosage requirement-a systematic review and meta analysis. Thrombosis Research, 125, e159-e166.