Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients. (12th September 2018)

• Record Type: Journal Article
• Authors: Maagdenberg, Hedy; Bierings, Marc B; van Ommen, C Heleen; van der Meer, Felix JM; Appel, Inge M; Tamminga, Rienk YJ; Cessie, Saskia le; Swen, Jesse J; der Straaten, Tahar van; Boer, Anthonius de; Maitland-van der Zee, Anke H
• Is Part Of: Pharmacogenomics. Volume 19:Number 15(2018)
• Page Start: 1195
• Page End: 1202
• Publication Date: 2018-09-12
• Subjects: adolescent -- anticoagulation -- child -- infant -- pharmacogenomics -- phenprocoumon -- thrombosis; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2018-0095
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm.Methods: Pediatric patients who used phenprocoumon were invited to participate in a retrospective follow-up study. Clinical information and genotypes of genetic variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and tested with linear regression for association with phenprocoumon dose requirement.Results: Of the 41 patients included in the analysis, age, VKORC1, CYP2C9*2/*3 and CYP3A4*1B were statistically significantly associated with dose requirement, and together explained 80.4% of the variability in phenprocoumon dose requirement.Conclusion: Our study reveals that age and genetic variations explain a significant part of the variability in phenprocoumon dose requirement in pediatric patients.