Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients

Hedy Maagdenberg; Marc B. Bierings; C. Heleen Van Ommen; Felix J.M. Van Der Meer; Inge M. Appel; Rienk Y.J. Tamminga; Saskia Le Cessie; Jesse J. Swen; Tahar Van Der Straaten; Anthonius De Boer; Anke H. Maitland-Van Der Zee

doi:10.2217/pgs-2018-0095

Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients

Hedy Maagdenberg, Marc B. Bierings, C. Heleen Van Ommen, Felix J.M. Van Der Meer, Inge M. Appel, Rienk Y.J. Tamminga, Saskia Le Cessie, Jesse J. Swen, Tahar Van Der Straaten, Anthonius De Boer, Anke H. Maitland-Van Der Zee

Department of Pediatric Stem Cell Transplantation, Princess Maxima Center for Pediatric Oncology, Wilhelmina Children's Hospital, University Medical Center Utrecht
Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Erasmus University Medical Center
Department of Thrombosis and Hemostasis, Leiden University Medical Center
Department of Pediatric Hematology, University Medical Center Groningen
Academic Medical Center

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1195-1202
Number of pages	8
Journal	Pharmacogenomics
Volume	19
Issue number	15
DOIs	https://doi.org/10.2217/pgs-2018-0095
Publication status	Published - 1 Oct 2018

Keywords

adolescent
anticoagulation
child
infant
pharmacogenomics
phenprocoumon
thrombosis
article
clinical article
controlled study
drug therapy
female
follow up
genetic variation
genotype
human
linear regression analysis
male
pediatric patient
retrospective study
cytochrome P450 2C18
cytochrome P450 2C9
cytochrome P450 3A4
endogenous compound

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pgs-2018-0095Final published version, 574 KBLicence: Taverne

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Maagdenberg, H., Bierings, M. B., Van Ommen, C. H., Van Der Meer, F. J. M., Appel, I. M., Tamminga, R. Y. J., Cessie, S. L., Swen, J. J., Van Der Straaten, T., De Boer, A., & Maitland-Van Der Zee, A. H. (2018). Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients. Pharmacogenomics, 19(15), 1195-1202. https://doi.org/10.2217/pgs-2018-0095

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title = "Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients",

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.",

keywords = "adolescent, anticoagulation, child, infant, pharmacogenomics, phenprocoumon, thrombosis, article, clinical article, controlled study, drug therapy, female, follow up, genetic variation, genotype, human, linear regression analysis, male, pediatric patient, retrospective study, cytochrome P450 2C18, cytochrome P450 2C9, cytochrome P450 3A4, endogenous compound",

author = "Hedy Maagdenberg and Bierings, {Marc B.} and {Van Ommen}, {C. Heleen} and {Van Der Meer}, {Felix J.M.} and Appel, {Inge M.} and Tamminga, {Rienk Y.J.} and Cessie, {Saskia Le} and Swen, {Jesse J.} and {Van Der Straaten}, Tahar and {De Boer}, Anthonius and {Maitland-Van Der Zee}, {Anke H.}",

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doi = "10.2217/pgs-2018-0095",

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Maagdenberg, H, Bierings, MB, Van Ommen, CH, Van Der Meer, FJM, Appel, IM, Tamminga, RYJ, Cessie, SL, Swen, JJ, Van Der Straaten, T, De Boer, A & Maitland-Van Der Zee, AH 2018, 'Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients', Pharmacogenomics, vol. 19, no. 15, pp. 1195-1202. https://doi.org/10.2217/pgs-2018-0095

TY - JOUR

T1 - Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients

AU - Maagdenberg, Hedy

AU - Bierings, Marc B.

AU - Van Ommen, C. Heleen

AU - Van Der Meer, Felix J.M.

AU - Appel, Inge M.

AU - Tamminga, Rienk Y.J.

AU - Cessie, Saskia Le

AU - Swen, Jesse J.

AU - Van Der Straaten, Tahar

AU - De Boer, Anthonius

AU - Maitland-Van Der Zee, Anke H.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

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KW - anticoagulation

KW - child

KW - infant

KW - pharmacogenomics

KW - phenprocoumon

KW - thrombosis

KW - article

KW - clinical article

KW - controlled study

KW - drug therapy

KW - female

KW - follow up

KW - genetic variation

KW - genotype

KW - human

KW - linear regression analysis

KW - male

KW - pediatric patient

KW - retrospective study

KW - cytochrome P450 2C18

KW - cytochrome P450 2C9

KW - cytochrome P450 3A4

KW - endogenous compound

U2 - 10.2217/pgs-2018-0095

DO - 10.2217/pgs-2018-0095

M3 - Article

SN - 1462-2416

VL - 19

SP - 1195

EP - 1202

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 15

ER -

Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients

Abstract

Keywords

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