Improvements in CYP2C9 Genotyping Accuracy Are Needed: A Report of the First Proficiency Testing for Warfarin-related CYP2C9 and VKORC1 Genotyping in China.

Abstract Warfarin is the most commonly used oral anticoagulant in clinical practice. The cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) genotypes have been confirmed to be associated with warfarin dose requirements. Accurate genotyping results are of particular importance for obtaining reliable genotype-guided warfarin dosing information. This study aims to determine analytic performance of laboratories offering CYP2C9 and VKORC1 testing in China. A proficiency panel of 15 validated cell samples covering common CYP2C9 and VKORC1 genetic polymorphisms was provided to 31 participating laboratories, and their genotyping results were evaluated. Fourteen data sets (45.2%) performed well with the entire panel of samples, and 17 data sets (54.8%) reported at least one genotyping error. For VKORC1 (-1639G>A), participating laboratories were 100% successful in detecting genotypes of GG, GA, and AA. For CYP2C9, participants were greater than 90% successful in detecting genotypes of *1/*1, *1/*2, *1/*3, *2/*3, and *3/*3. However, 15 laboratories failed to detect rarely encountered variant genotype *2/*2. The poor performance of CYP2C9 genotyping may be because of the limitation of methodologies used for detecting CYP2C9*2 allele. The proficiency testing survey highlighted the need for improving genotyping accuracy for some laboratories in this field.