title: 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.
authors: *National Center for Clinical Laboratories, Beijing Hospital, Beijing, China; and †Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors: Guigao
authors: G
authors: Lin
authors: Lang
authors: L
authors: Yi
authors: Kuo
authors: K
authors: Zhang
authors: Yu
authors: Y
authors: Sun
authors: Lunan
authors: L
authors: Wang
authors: Rui
authors: R
authors: Zhang
authors: Jiehong
authors: J
authors: Xie
authors: Jinming
authors: J
authors: Li
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects; D002460:Cell Line; D002681:China; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced / Q000235:genetics; D006801:Humans; D019934:International Normalized Ratio / Q000592:standards; D059021:Laboratory Proficiency Testing / Q000592:standards*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D016037:Single-Blind Method; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases