An anticoagulant with a narrow therapeutic index, whose effective dose differs several-fold between people. More of that variation is explained by genotype than for almost any other drug in common use.
VKORC1 encodes vitamin K epoxide reductase, the direct target of warfarin. The rs9923231 (c.-1639G>A) variant sits on a haplotype that changes how much VKORC1 protein is produced. Carrying one or two copies of the -1639A allele is associated with progressively lower warfarin dose requirements compared with -1639G/G, and CPIC describes the A/A genotype as increased warfarin sensitivity. CPIC does not define named metabolizer phenotypes for VKORC1 — laboratories report the genotype with a sensitivity interpretation. Common VKORC1 variants account for up to about 30% of the variance in stable dose in European-ancestry patients. No dose guidance is given here; warfarin is managed by a prescriber with INR monitoring.
CPIC Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Johnson JA et al. Clin Pharmacol Ther. 2017;102(3):397-404 (PMID 28198005).
CYP2C9 is the main enzyme clearing S-warfarin, the more potent form of the drug. Decreased-function star alleles — most commonly *2 and *3, plus *5, *6, *8 and *11 which are more frequent in African-ancestry populations — reduce that clearance. CPIC classifies CYP2C9 diplotypes into normal, intermediate and poor metabolizer phenotypes. Published studies associate carriage of reduced-function alleles with greater bleeding risk on warfarin and longer time to a stable INR. This gene is part of the CPIC guideline but is not currently reported by MyGeneLog.
CPIC Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Johnson JA et al. Clin Pharmacol Ther. 2017;102(3):397-404 (PMID 28198005).
CYP4F2 oxidises vitamin K and removes it from the vitamin K cycle, acting as a counterweight to VKORC1. The CYP4F2*3 variant (rs2108622) has a modest effect, with meta-analyses indicating roughly 8-11% higher dose requirements in carriers. The association is supported in European and Asian ancestry populations but not in African ancestry populations. Included in the CPIC guideline; not currently reported by MyGeneLog.
CPIC Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Johnson JA et al. Clin Pharmacol Ther. 2017;102(3):397-404 (PMID 28198005).
These are the positions in your own file that carry the genes above. Not every gene in a guideline is one we report — where that is the case the gene appears above without a variant here, and the note says so.