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首页> 外文期刊>Clinical and applied thrombosis/hemostasis : >Influence of VKORC1 and CYP2C9 Polymorphisms on Daily Acenocoumarol Dose Requirement in South Indian Patients With Mechanical Heart Valves
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Influence of VKORC1 and CYP2C9 Polymorphisms on Daily Acenocoumarol Dose Requirement in South Indian Patients With Mechanical Heart Valves

机译：VKORC1和CYP2C9多态性对印度南部机械心脏瓣膜患者每日Acenocoumarol剂量需求的影响

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Chronic rheumatic heart disease (RHD) patients who undergo valve replacement with mechanical valves require lifelong anticoagulation. Acenocoumarol, a vitamin K antagonist has a narrow therapeutic range and wide inter-individual variability. Our aim was to investigate the influence of polymorphisms of VKORC1 and CYP2C9 genes on the mean daily dose requirement of acenocoumarol. 205 chronic RHD patients, with mechanical heart valves and on acenocoumarol therapy, were recruited. Genotyping for VKORC1 (?1639GA and 1173CT) and CYP2C9 (*2 & *3 alleles) polymorphisms was done by PCR-RFLP. There was complete linkage disequilibrium between VKORC1 polymorphisms (r2 = 0.98, D′ = 1.0, LOD = 74.02). VKORC1 genotype distribution for GG/CC, GA/CT, and AA/TT were 57.6%, 36.1%, and 6.3%, respectively. CYP2C9 genotype distribution for *1/*1, *1/*3, *1/*2, *2/*2, and *2/*3 were 78.5%, 14.1%, 6.3%, 0.5%, and 0.5%, respectively. Patients with a wild type of both VKORC1 (?1639GG and 1173CC) and CYP2C9 gene variants required higher acenocoumarol dose compared to those with mutant genotype (P = 0.023 and P = 0.008 respectively). On combined genotype analysis, patients having a combination of wild type of VKORC1 with wild type of CYP2C9 (44.4%) required higher daily dose compared to patients bearing heterozygous VKORC1 (?1639GA & 1173CT) with wild type of CYP2C9 (30.2%, P = 0.008). Presence of a mutant allele of VKORC1 (?1639A & 1173T) and CYP2C9 genes increased the odds of requiring a lower mean dosage of acenocoumarol. Studying the combination of genotypes in RHD patients could predict acenocoumarol dose requirement more accurately.
机译：进行机械瓣膜置换的慢性风湿性心脏病（RHD）患者需要终生抗凝治疗。维生素K拮抗剂Acenocoumarol具有较窄的治疗范围和广泛的个体差异。我们的目的是研究VKORC1和CYP2C9基因多态性对乙酰甲香豆酚日均剂量需求的影响。招募了205名患有机械性心脏瓣膜并接受乙酰香豆酚治疗的RHD慢性患者。通过PCR-RFLP对VKORC1（？1639G> A和1173C> T）和CYP2C9（* 2和* 3等位基因）多态性进行基因分型。 VKORC1多态性之间完全连锁不平衡（r2 = 0.98，D'= 1.0，LOD = 74.02）。 GG / CC，GA / CT和AA / TT的VKORC1基因型分布分别为57.6％，36.1％和6.3％。 * 1 / * 1，* 1 / * 3，* 1 / * 2，* 2 / * 2和* 2 / * 3的CYP2C9基因型分布分别为78.5％，14.1％，6.3％，0.5％和0.5％ ， 分别。与突变基因型患者相比，具有VKORC1（？1639GG和1173CC）和CYP2C9基因变体的野生型患者需要更高的醋氨香豆酚剂量（分别为P = 0.023和P = 0.008）。在组合基因型分析中，与带有野生型CYP2C9的杂合子VKORC1（？1639GA＆1173CT）的患者相比，具有野生型VKORC1和野生型CYP2C9（44.4％）组合的患者需要更高的日剂量（30.2％，P = 0.008）。 VKORC1（？1639A和1173T）和CYP2C9基因的突变等位基因的存在增加了需要较低平均剂量的乙酰香豆酚的可能性。研究RHD患者的基因型组合可以更准确地预测乙酰香豆酚的剂量需求。

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