Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose
Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose
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DOI：
10.1056/nejmoa044503
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发表时间：
2005-06-02
影响因子：
158.5
通讯作者：
Rettie, AE
中科院分区：
文献类型：
--
作者：
Rieder, MJ;Reiner, AP;Rettie, AE
背景：华法林治疗的管理因患者之间药物反应的广泛差异而变得复杂。基因编码的维生素K环氧化物还原酶复合物1（VKORC 1）的变异可能会影响华法林的反应。方法：我们进行了一项回顾性研究，欧洲，美国患者接受长期华法林维持治疗。采用多元线性回归分析确定VKORC 1单倍型对华法林剂量的影响。我们确定了VKORC 1单倍型频率在非洲裔美国人，欧洲裔美国人和亚裔美国人的人口和VKORC 1信使RNA（mRNA）在人类肝脏samples.RESULTS表达：我们确定了10个常见的非编码VKORC 1单核苷酸多态性，并推断出五个主要的单倍型。我们鉴定了低剂量单倍型组（A）和高剂量单倍型组（B）。华法林的平均（+/-SE）维持剂量在三种单倍型组组合中有显著差异，A/A为2.7+/-0.2 mg/天，A/B为4.9+/-0.2 mg/天，B/B为6.2+/-0.3 mg/天（P
BACKGROUND:The management of warfarin therapy is complicated by a wide variation among patients in drug response. Variants in the gene encoding vitamin K epoxide reductase complex 1 (VKORC1) may affect the response to warfarin.METHODS:We conducted a retrospective study of European-American patients receiving long-term warfarin maintenance therapy. Multiple linear-regression analysis was used to determine the effect of VKORC1 haplotypes on the warfarin dose. We determined VKORC1 haplotype frequencies in African-American, European-American, and Asian-American populations and VKORC1 messenger RNA (mRNA) expression in human liver samples.RESULTS:We identified 10 common noncoding VKORC1 single-nucleotide polymorphisms and inferred five major haplotypes. We identified a low-dose haplotype group (A) and a high-dose haplotype group (B). The mean (+/-SE) maintenance dose of warfarin differed significantly among the three haplotype group combinations, at 2.7+/-0.2 mg per day for A/A, 4.9+/-0.2 mg per day for A/B, and 6.2+/-0.3 mg per day for B/B (P