Qazim Berisha, Stöllberger Claudia, Krugluger Walter, Dossenbach-Glaninger Astrid, Finsterer Josef
Second Medical Department, Krankenanstalt Rudolfstiftung, Vienna, Austria.
J Thromb Thrombolysis. 2009 Aug;28(2):211-4. doi: 10.1007/s11239-008-0252-8. Epub 2008 Jul 16.
Polymorphisms in the vitamin K epoxide-reductase-complex-1 (VKORC1) and the cytochrome-P450-isozyme (CYP2C9) genes account for therapeutic responses to vitamin K antagonists (VKA). This study aimed to investigate the prevalence of VKORC1 and CYP2C9 polymorphisms among patients under phenprocoumon and its influence on the VKA dosage.
Patients under phenprocoumon were screened for the polymorphisms -1639G > A and 3730G > A in the VKORC1 gene and 430C > T and 1075A > C in the CYP2C9 gene by means of a StripAssay. Baseline clinical and laboratory parameters were registered.
Among 53 patients (28 females, mean age 72.5 years), VKORC1 polymorphisms were found in 34 [-1639G > A: homozygote (n = 11), heterozygote (n = 23)] and 28 [3730G > A: homozygote (n = 7), heterozygote (n = 21)] patients. Thirteen patients were compound heterozygote. CYP2C9 polymorphisms were found in 12 [430G > T: homozygote (n = 1), heterozygote (n = 11)] and 7 [1075A > C: homozygote (n = 0), heterozygote (n = 7)] patients. Seventeen patients had at least one VKORC1 and one CYP2C9 polymorphism. Mean phenprocoumon dosage per week to achieve therapeutic anticoagulation was lower (higher) in patients with than without the VKORC1 polymorphism -1639G > A (3730G > A) or the CYP2C9 polymorphisms. Despite the presence of VKORC1 or CYP2C9 polymorphisms, mean International Normalized Ratio was not significantly different between patients with and without polymorphisms.
Though VKORC1 and CYP2C9 polymorphisms influence the phenprocoumon dosage necessary to achieve therapeutic anticoagulation, anticoagulation is therapeutic if carefully monitored.
维生素K环氧化物还原酶复合体1（VKORC1）和细胞色素P450同工酶（CYP2C9）基因多态性可解释维生素K拮抗剂（VKA）的治疗反应。本研究旨在调查接受苯丙香豆素治疗患者中VKORC1和CYP2C9基因多态性的发生率及其对VKA剂量的影响。
采用条带分析法对接受苯丙香豆素治疗的患者进行VKORC1基因-1639G>A和3730G>A以及CYP2C9基因430C>T和1075A>C多态性的筛查。记录基线临床和实验室参数。
在53例患者（28例女性，平均年龄72.5岁）中，34例患者发现VKORC1基因多态性[-1639G>A：纯合子（n=11），杂合子（n=23）]，28例患者发现3730G>A多态性[纯合子（n=7），杂合子（n=21）]。13例患者为复合杂合子。12例患者发现CYP2C9基因多态性[430G>T：纯合子（n=1），杂合子（n=11）]，7例患者发现1075A>C多态性[纯合子（n=0），杂合子（n=7）]。17例患者至少有1种VKORC1和1种CYP2C9基因多态性。与未发生VKORC1基因-1639G>A（3730G>A）或CYP2C9基因多态性的患者相比，发生这些多态性的患者达到治疗性抗凝所需的每周平均苯丙香豆素剂量较低（较高）。尽管存在VKORC1或CYP2C9基因多态性，但有和没有多态性的患者之间平均国际标准化比值无显著差异。
虽然VKORC1和CYP2C9基因多态性会影响达到治疗性抗凝所需的苯丙香豆素剂量，但如果仔细监测，抗凝治疗是有效的。
