Rathore S S, Agarwal S K, Pande S, Mittal T, Mittal B
Departments of Genetics and CVTS.
Indian J Hum Genet. 2011 May;17 Suppl 1(Suppl 1):S54-7. doi: 10.4103/0971-6866.80360.
The dose requirements for oral anticoagulants in thromboembolic events are influenced by promoter polymorphism in the VKORC1 gene. However, limited data are available on the influence of the polymorphism in various Indian populations. The present study aimed at determining the relationship between the VKORC1-1639 G>A genotypes and maintenance doses of oral anticoagulants for therapeutically stable INR values in patients taking Acitrom after valve replacement surgery.
Fifty patients from the northern Indian region were genotyped for VKORC1-1639 G>A by polymerase chain reaction and restriction fragment length polymorphism. Means of the weight-normalized daily Acitrom dose were calculated for every patient.
The VKORC1 1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity.1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity.
The VKORC1-1639 G>A status can be indicative of establishing the therapeutic dose of oral anticoagulants in Indian patients.
血栓栓塞事件中口服抗凝剂的剂量需求受维生素K环氧化物还原酶复合体亚单位1（VKORC1）基因启动子多态性影响。然而，关于该多态性在不同印度人群中的影响的数据有限。本研究旨在确定VKORC1 - 1639G>A基因型与瓣膜置换术后服用醋硝香豆素患者达到治疗稳定国际标准化比值（INR）值时口服抗凝剂维持剂量之间的关系。
采用聚合酶链反应和限制性片段长度多态性方法对来自印度北部地区的50例患者进行VKORC1 - 1639G>A基因分型。计算每位患者体重标准化的每日醋硝香豆素剂量均值。
研究人群（n = 50）中VKORC1 1639G>A次要等位基因频率为22%。野生型基因型患者需要酶完全发挥功能时建议的最大药物剂量。杂合子患者的药物剂量处于中间水平，而变异纯合子基因型患者的维持药物剂量需求最低。这些发现与启动子多态性对维生素K环氧化物还原酶活性的影响一致。研究人群（n = 50）中VKORC1 1639G>A次要等位基因频率为22%。野生型基因型患者需要酶完全发挥功能时建议的最大药物剂量。杂合子患者的药物剂量处于中间水平，而变异纯合子基因型患者的维持药物剂量需求最低。这些发现与启动子多态性对维生素K环氧化物还原酶活性的影响一致。
VKORC1 - 1639G>A状态可用于指导确定印度患者口服抗凝剂的治疗剂量。
