Oner Ozgon G, Langaee T Y, Feng H, Buyru N, Ulutin T, Hatemi A C, Siva A, Saip S, Johnson J A
University of Istanbul, Istanbul, Turkey.
Eur J Clin Pharmacol. 2008 Sep;64(9):889-94. doi: 10.1007/s00228-008-0507-5. Epub 2008 Jun 10.
The objective of this study was to determine the quantitative influence of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP 2C9) polymorphisms on warfarin dose requirements in Turkish patients.
A total of 205 patients taking warfarin for >2 months were enrolled in the study. Deoxyribonucleic acid (DNA) samples from these patients were genotyped for polymorphisms in VKORC1 and CYP2C9 genes. A linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on mean warfarin dose requirements.
The VKORC1 promoter polymorphism (3673 G>A) was associated with differences in weekly mean varfarin dose: for GG genotype the dose was 43.18 mg/week, for GA genotype 33.78 mg/week and for AA genoype 25.83 mg/week (P < 0.0001). Patients who carried VKORC1 and CYP2C9 variants needed a 40% lower mean weekly warfarin dose compared to wild types. Variables associated with lower warfarin dose requirements were VKORC1 3673 AA or GA genotype (both P < 0.0001), one or two CYP2C9 variant alleles (both P < 0.0001), increasing age (P < 0.0001) and non-indication of venous thromboembolism for warfarin therapy (P = 0.002).
Polymorphisms in VKORC1 and CYP2C9 genes were important determinants of warfarin dose requirements in Turkish patients.
本研究的目的是确定维生素K环氧化物还原酶复合体亚基1（VKORC1）和细胞色素P450 2C9（CYP 2C9）基因多态性对土耳其患者华法林剂量需求的定量影响。
共有205名服用华法林超过2个月的患者纳入本研究。对这些患者的脱氧核糖核酸（DNA）样本进行VKORC1和CYP2C9基因多态性基因分型。采用线性回归分析确定遗传和非遗传因素对华法林平均剂量需求的独立影响。
VKORC1启动子多态性（3673 G>A）与每周平均华法林剂量差异相关：GG基因型剂量为43.18毫克/周，GA基因型为33.78毫克/周，AA基因型为25.83毫克/周（P<0.0001）。与野生型相比，携带VKORC1和CYP2C9变异体的患者平均每周华法林剂量需求低40%。与较低华法林剂量需求相关的变量包括VKORC1 3673 AA或GA基因型（均P<0.0001）、一个或两个CYP2C9变异等位基因（均P<0.0001）、年龄增加（P<0.0001）以及华法林治疗无静脉血栓栓塞指征（P=0.002）。
VKORC1和CYP2C9基因多态性是土耳其患者华法林剂量需求的重要决定因素。
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