Wypasek Ewa, Cieśla Marek, Suder Bogdan, Janik Łukasz, Sadowski Jerzy, Undas Anetta
John Paul II Hospital, Institute of Cardiology, Jagiellonian University School of Medicine, Kraków, Poland.
John Paul II Hospital, Kraków, Poland.
Adv Clin Exp Med. 2015 Jul-Aug;24(4):607-14. doi: 10.17219/acem/32577.
Warfarin dose requirements are partly determined by common single nucleotide polymorphisms in VKORC1 and CYP2C9 genes.
The aim of this study was to investigate how the presence of allelic variants in CYP2C9 affects the stability of anticoagulation in patients within the first 3 months following elective heart valve replacement.
In a case-control study we compared 18 consecutive carriers of CYP2C9*2 and/or 3 and 25 well-matched patients with the wild type CYP2C91/*1 genotype. The former group was randomly assigned to use coagulometers or monitor international normalized ratio (INR) in local outpatient clinics. Subjects receiving drugs potently interfering with warfarin were ineligible. Anticoagulation with the baseline warfarin regimens based on pharmacogenetic algorithm was assessed by time in the therapeutic INR range (TTR) within the first 3 months following implantation.
Carriers of the CYP2C9*2 and/or 3 genotypes were characterized by lower estimated warfarin dose (median, 21 [interquartile range, 21-35] vs. 35 [28-42] mg/week, p=0.02) and actual (27.8±13.2 vs. 46.3±13.9 mg/week, p<0.001), together with lower TTR values (56 [38.6-74.9] vs. 75.4 [58.1-83.6] %, p=0.03) and longer time above the therapeutic range (13.8 [4.9-34.5] vs. 4.5 [0-15.3]%, p=0.047) than patients with the CYP2C91/*1 genotype. There were no differences in the estimated and actual warfarin doses, TTR values and adverse events between the self-testing and standard-care subgroups.
The presence of CYP2C9*2 and/or *3 genotypes is associated with unstable warfarin treatment in patients after heart valve replacement, regardless of the type of INR testing.
华法林的剂量需求部分由维生素K环氧化物还原酶复合体1（VKORC1）和细胞色素P450 2C9（CYP2C9）基因中的常见单核苷酸多态性决定。
本研究旨在调查CYP2C9等位基因变异的存在如何影响择期心脏瓣膜置换术后3个月内患者抗凝的稳定性。
在一项病例对照研究中，我们比较了18例连续的CYP2C92和/或3携带者以及25例匹配良好的野生型CYP2C9*1/*1基因型患者。前一组被随机分配使用凝血仪或在当地门诊监测国际标准化比值（INR）。接受强效干扰华法林药物治疗的受试者不符合条件。在植入后的前3个月内，通过治疗性INR范围内的时间（TTR）评估基于药物遗传学算法的基线华法林治疗方案的抗凝效果。
CYP2C92和/或3基因型携带者的华法林估计剂量较低（中位数，21[四分位间距，21 - 35]对比35[28 - 42]mg/周，p = 0.02）和实际剂量较低（27.8±13.2对比46.3±13.9mg/周，p < 0.001），同时TTR值较低（56[38.6 - 74.9]对比75.4[58.1 - 83.6]%，p = 0.03），高于治疗范围的时间较长（13.8[4.9 - 34.5]对比4.5[0 - 15.3]%，p = 0.047），均高于CYP2C9*1/*1基因型患者。自我检测和标准护理亚组之间在华法林估计剂量和实际剂量、TTR值及不良事件方面没有差异。
CYP2C92和/或3基因型的存在与心脏瓣膜置换术后患者华法林治疗不稳定相关，与INR检测类型无关。
