Annotation of rs9923231

Genotype CC is associated with increased dose of warfarin in children with Heart Diseases as compared to genotype TT.

A model was created to predict maintenance doses for children of different ages, all with a baseline INR of 1 and a target INR of 2.5, based on longitudinal data from children taking warfarin. A two-fold difference in dose between children with the CC and TT genotype was found. A table predicting warfarin dose for children of 2, 8 and 14 years old with different rs9923231 genotype and CYP2C9 genotype is presented in the paper. CYP2C9 genotype, VKORC1 genotype, bodyweight, age, baseline INR, target INR and time since initiation of therapy were all found to be significant causes of warfarin dose variability in children. Note: alleles have been complemented to the plus chromosomal strand.

From Publication

Characterizing variability in warfarin dose requirements in children using modelling and simulation. British journal of clinical pharmacology. 2014. Hamberg Anna-Karin et al.
PMID:24330000(opens in new window) PMCID:PMC4168390(opens in new window) DOI:10.1111/bcp.12308(opens in new window)

Gene

VKORC1

Variant

rs9923231

Phenotype Category

Dosage, Efficacy

Association Significance

The study reports this association is significant

Specialty Population

PediatricLearn more about pediatric tags(opens in new window)

PharmGKB ID

1184654330

Score
More info on scoring

1.5

Evidence for Clinical Annotations

This annotation has been used as evidence for the following clinical annotations.

    Study Parameters

    Study type

    cohort

    Study size

    163

    Allele frequency

    T=0.41

    Population description

    children (pediatrics)

    Study Cohort: Children with underlying heart disease recruited from hospitals in the UK, Canada and Sweden.

    Note: Alleles in PharmGKB are mapped to the positive chromosomal strand. Therefore, variants in genes on the "minus" strand (eg. VKORC1) are complemented in PharmGKB annotations.

    History

    No history available.