Warfarin is the most commonly used anticoagulant in the clinical treatment of thromboembolic diseases. The dose of warfarin varies significantly within populations, and the dose is closely related to the genetic polymorphisms of the CYP2C9 and VKORC1 genes. In this study, a new CYP2C9 nonsynonymous mutation (8576C > T) was detected after the genetic screening of 162 patients took warfarin. This mutation, named as the new allele CYP2C9*62, can result in an arginine to cysteine amino acid substitution at position 125 of the CYP2C9 protein (R125C). When expressed in insect cells, the protein expression of CYP2C9.62 was significantly lower than that of the wild-type, and its metabolic activity was also significantly decreased after the addition of three typical CYP2C9 probe drugs, suggesting that the new mutant can dramatically affect the metabolism of CYP2C9 drugs in vitro.

华法林是血栓栓塞性疾病临床治疗中最常用的抗凝剂。华法林的剂量在人群中变化很大，并且剂量与CYP2C9和VKORC1基因的遗传多态性密切相关。在这项研究中，对162名服用华法林的患者进行了基因筛查后，发现了一个新的CYP2C9非同义突变（8576C> T）。该突变名为新等位基因CYP2C9 * 62可能导致CYP2C9蛋白（R125C）第125位的精氨酸变为半胱氨酸氨基酸。当在昆虫细胞中表达时，CYP2C9.62的蛋白表达显着低于野生型，并且在加入三种典型的CYP2C9探针药物后其代谢活性也显着降低，表明该新突变体可以显着影响CYP2C9药物的体外代谢。