Ozer Nihat, Cam Nese, Tangurek Burak, Ozer Songul, Uyarel Huseyin, Oz Dilaver, Guney Mehmet Rasit, Ciloglu Figen
Selami Ali Mah. Bakkaladem Sok. Gedikoglu Apt. No: 6/6, Uskudar, Istanbul, 34600, Turkey.
Heart Vessels. 2010 Mar;25(2):155-62. doi: 10.1007/s00380-009-1177-7. Epub 2010 Mar 26.
In this study, we investigated the contribution of vitamin K epoxide reductase (VKORC1) and cytochrome P450 2C9 (CYP2C9) genotypes, age, and body surface area (BSA) on warfarin dose requirements and in an adult Turkish population. Blood samples were collected from 100 Turkish patients with stable warfarin dose requirements and an international normalized ratio (INR) of the prothrombin time within the therapeutic range. Genetic analyses for CYP2C9 genotypes (*2 and *3 alleles) and VKORC1 -1639 G>A polymorphism were performed and venous INR determined. The mean warfarin daily dose requirement was higher in CYP2C9 homozygous wild-type patients, compared to those with the variant *3 allele (P < 0.05), similar to those with the variant *2 allele (P > 0.05) and highest in patients with the VKORC1 -1639 GG genotype compared to those with the GA genotype and the AA genotype (P < 0.01). The time to therapeutic INR was longer in CYP2C9 homozygous wild-type patients compared with those with the variant *2 and *3 alleles (P < 0.01), and longer in patients with the VKORC1 (position -1639) GG genotype compared with those with the GA genotype and the AA genotype (P < 0.01). The multivariate regression model including the variables of age (R (2) = 4.4%), BSA (R (2) = 27.4%), CYP2C9 (R (2) = 8.1%), and VKORC1 genotype (R (2) = 34.1%) produced the best model for estimating warfarin dose (R (2) = 60.4%). VKORC1 genotype and CYP2C9 polymorphism affect daily dose requirements and time to therapeutic INR in Turkish patients receiving warfarin for anticoagulation.
在本研究中，我们调查了维生素K环氧化物还原酶（VKORC1）和细胞色素P450 2C9（CYP2C9）基因型、年龄以及体表面积（BSA）对成人土耳其人群华法林剂量需求的影响。从100名华法林剂量需求稳定且凝血酶原时间国际标准化比值（INR）在治疗范围内的土耳其患者中采集血样。进行了CYP2C9基因型（2和3等位基因）和VKORC1 -1639 G>A多态性的基因分析，并测定静脉INR。与携带3等位基因变异的患者相比，CYP2C9纯合野生型患者的平均每日华法林剂量需求更高（P < 0.05），与携带*2等位基因变异的患者相似（P > 0.05）；与携带GA基因型和AA基因型的患者相比，携带VKORC1 -1639 GG基因型的患者平均每日华法林剂量需求最高（P < 0.01）。与携带2和*3等位基因变异的患者相比，CYP2C9纯合野生型患者达到治疗性INR的时间更长（P < 0.01）；与携带GA基因型和AA基因型的患者相比，携带VKORC1（位置 -1639）GG基因型的患者达到治疗性INR的时间更长（P < 0.01）。包含年龄（R (2) = 4.4%）、BSA（R (2) = 27.4%）、CYP2C9（R (2) = 8.1%）和VKORC1基因型（R (2) = 34.1%）变量的多元回归模型产生了估算华法林剂量的最佳模型（R (2) = 60.4%）。VKORC1基因型和CYP2C9多态性影响接受华法林抗凝治疗的土耳其患者的每日剂量需求和达到治疗性INR的时间。
