Comparison of performance of three commercial platforms for warfarin sensitivity genotyping.
BACKGROUND
We performed a 3-way comparison on the Osmetech eSensor, AutoGenomics INFINITI, and a real-time PCR method (Paragonx reagents/Stratagene RT-PCR platform) for their FDA-cleared warfarin panels, and additional polymorphisms (CYP2C9*5, *6, and 11 and extended VKORC1 panels) where available.


METHODS
One hundred de-identified DNA samples were used in this IRB-approved study. Accuracy was determined by comparison of genotyping results across three platforms. Any discrepancy was resolved by bi-directional sequencing. The CYP4F2 on Osmetech was validated by bi-directional sequencing.


RESULTS
Accuracies for CYP2C9*2 and *3 were 100% for all 3 platforms. VKORC1 3673 genotyping accuracies were 100% on eSensor and 97% on Infiniti. CYP2C9*5, *6 and *11 showed 100% concordance between eSensor and Infiniti. VKORC1 6484 and 9041 variants compared between ParagonDx and Infiniti analyzer were 100% (6484) and 99% (9041) concordant. CYP4F2 was 100% concordant with sequencing results. The time required to generate the results from automated DNA extraction-to-result was approximately 8h on Infiniti, and 4h on eSensor and ParagonDx, respectively.


CONCLUSIONS
Overall, we observed excellent CYP2C9*2 and *3 genotyping accuracy for all three platforms. For VKORC1 3673 genotyping, eSensor demonstrated a slightly higher accuracy than the Infiniti, and CYP4F2 on Osmetech was 100% accurate.
Babic
Nikolina
N
Department of Pathology, Pritzker School of Medicine, The University of Chicago, 5481 S. Maryland Avenue, Chicago, IL 60637, United States.
Haverfield
Eden V
EV
Burrus
Julie A
JA
Lozada
Anthony
A
Das
Soma
S
Yeo
Kiang-Teck J
KT
D000925:Anticoagulants / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D005838:Genotype; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014481:United States; D014486:United States Food and Drug Administration; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000494:pharmacology*
D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases