The objective of this study is to estimate the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants and their contribution to warfarin dose variability in Qataris. One hundred and fifty warfarin-treated Qatari patients on a stable dose and with a therapeutic INR for at least three consecutive clinic visits were recruited. Saliva samples were collected using Oragene DNA self-collection kit, followed by DNA purification and genotyping via TaqMan Real-Time-PCR assay. The population was stratified into derivation and validation cohorts for the dosing model. The minor allele frequency (MAF) of VKORC1 (−1639G>A) was A (0.47), while the MAF’s for the CYP2C9*2 and *3 and CYP4F2*3 were T (0.12), C (0.04) and T (0.43), respectively. Carriers of at least one CYP2C9 decreased function allele (*2 or *3) required lower median (IQR) warfarin doses compared to noncarriers [24.5 (14.5) mg/week vs. 35 (21) mg/week, p < 0.001]. Similarly, carriers of each additional copy of (A) variant in VKORC1 (−1639G>A) led to reduction in warfarin dose requirement compared to noncarriers [21(7.5) vs. 31.5(18.7) vs. 43.7(15), p < 0.0001]. CYP4F2*3 polymorphism on the other hand was not associated with warfarin dose. Multivariate analysis on the derivation cohort (n = 104) showed that a dosing model consisting of hypertension (HTN), heart failure (HF), VKORC1 (−1639G>A), CYP2C9*2 & *3, and smoking could explain 39.2% of warfarin dose variability in Qataris (P < 0.001). In the validation cohort (n = 45), correlation between predicted and actual warfarin doses was moderate (Spearman’s rho correlation coefficient = 0.711, p < 0.001). This study concluded that VKORC1 (−1639G>A), CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with HTN, HF and smoking.

这项研究的目的是估计VKORC1，CYP2C9和CYP4F2遗传变异的发生率及其对卡塔尔华法林剂量变异性的影响。招募了150名华法林治疗的卡塔尔患者，这些患者剂量稳定且至少连续3次就诊具有治疗性INR。使用Oragene DNA自收集试剂盒收集唾液样品，然后通过TaqMan Real-Time-PCR测定法进行DNA纯化和基因分型。总体分为剂量模型的派生和验证队列。VKORC1（−1639G> A）的次要等位基因频率（MAF）为A（0.47），而CYP2C9 * 2和* 3和CYP4F2的MAF为* 3分别是T（0.12），C（0.04）和T（0.43）。与非载体相比，至少一种CYP2C9降低功能等位基因（* 2或* 3）的载体需要更低的中值（IQR）华法林剂量[24.5（14.5）mg /周与35（21）mg /周，p  <0.001]。类似地，与非携带者相比，VKORC1（-1639G> A）中每个（A）变体的每一个额外拷贝的携带者导致华法林剂量需求的减少[21（7.5）vs. 31.5（18.7）vs. 43.7（15），p  < 0.0001]。另一方面，CYP4F2 * 3多态性与华法林剂量无关。对派生队列（n  = 104）的多变量分析表明，剂量模型由高血压（HTN），心力衰竭（HF），VKORC1组成（−1639G> A），CYP2C9 * 2和* 3和吸烟可以解释卡塔尔地区华法林剂量差异的39.2％（P  <0.001）。在验证队列中（n  = 45），华法林的预测剂量与实际剂量之间的相关性中等（Spearman的rho相关系数= 0.711，p  <0.001）。这项研究得出的结论是，VKORC1（−1639G> A），CYP2C9 * 2和* 3是华法林剂量以及HTN，HF和吸烟的最重要预测因子。