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The effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirements in a pediatric population

Birce Dilge Taşkın1, Serdar Kula2, Mehmet Ali Ergün3

  • 1Department of Pediatric Neurology, Ankara Children's Hematology Oncology Training and Research Hospital, Ankara-Turkey.

Anatolian Journal of Cardiology
|May 17, 2016
PubMed

Insights

Genetic variations in CYP2C9 and VKORC1 influence warfarin dosing in children. Identifying these genetic polymorphisms can help achieve target INRs and minimize complications in pediatric patients.

Area of Science:

  • Pharmacogenomics
  • Pediatric Medicine
  • Clinical Chemistry

Background:

  • Warfarin dosing requires careful management due to its narrow therapeutic index.
  • Genetic factors, specifically polymorphisms in CYP2C9 and VKORC1, are known to affect warfarin metabolism and efficacy.
  • Understanding these genetic influences is crucial for optimizing treatment in pediatric populations.

Purpose of the Study:

  • To determine the frequency of CYP2C9 and VKORC1 genetic polymorphisms in pediatric patients.
  • To evaluate the impact of these polymorphisms on warfarin dose requirements.
  • To correlate calculated ideal warfarin doses with administered doses based on genetic profiles.

Main Methods:

  • A prospective, observational study involving 58 pediatric patients on stable warfarin doses and 149 healthy controls.
  • Analysis of CYP2C9*2, CYP2C9*3, and VKORC1 polymorphisms using polymerase chain reaction techniques.
  • Calculation of ideal warfarin doses based on patient demographics and identified genetic polymorphisms, followed by statistical comparison with administered doses.

Main Results:

  • Frequencies of CYP2C9 and VKORC1 polymorphisms were established, with specific variant alleles identified in a significant portion of the patient cohort.
  • Pediatric patients with allelic variants of CYP2C9 and VKORC1 required significantly lower warfarin doses.
  • A strong correlation (64.5%) was observed between calculated ideal warfarin doses and actual administered doses when genetic polymorphisms were considered.

Conclusions:

  • CYP2C9 and VKORC1 genetic polymorphisms significantly impact warfarin dose requirements in pediatric patients.
  • Genotyping for these polymorphisms before initiating warfarin therapy can facilitate achieving therapeutic International Normalized Ratios (INRs).
  • Pre-treatment genetic screening may reduce the incidence of warfarin-related complications in children.
Abstract

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