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

^*Corresponding author for this work

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

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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",

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.\}",

year = "2018",

month = oct,

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

language = "English",

volume = "19",

pages = "1195--1202",

journal = "Pharmacogenomics",

issn = "1462-2416",

publisher = "Taylor and Francis Ltd.",

number = "15",

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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.

KW - adolescent

KW - anticoagulation

KW - child

KW - infant

KW - pharmacogenomics

KW - phenprocoumon

KW - thrombosis

UR - https://www.scopus.com/pages/publications/85054435251

U2 - 10.2217/pgs-2018-0095

DO - 10.2217/pgs-2018-0095

M3 - Article

C2 - 30207196

AN - SCOPUS:85054435251

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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