Genotyping three SNPs affecting warfarin drug response by isothermal real-time HDA assays.
Genotyping three SNPs affecting warfarin drug response by isothermal real-time HDA assays.
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DOI：
10.1016/j.cca.2010.09.014
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发表时间：
2011-01-14
期刊：
影响因子：
--
通讯作者：
Kong H
中科院分区：
文献类型：
--
作者：
Li Y;Jortani SA;Ramey-Hartung B;Hudson E;Lemieux B;Kong H
对抗凝药物华法林的反应受VKORC 1和CYP 2C 9基因的遗传多态性影响很大。基因分型这些多态性已被证明是重要的，在减少时间的试验和错误的过程中找到维持剂量的华法林，从而降低药物的不良反应的风险。我们开发了一种实时等温DNA扩增系统，用于基因分型三个单核苷酸多态性（SNPs），影响华法林的反应。对于每个SNP，进行实时等温解旋酶依赖性扩增（HDA）反应以扩增含有SNP的DNA片段。在实时HDA扩增期间通过荧光标记的等位基因特异性探针检测扩增子。通过基于HDA的方法分析了50份临床样本，共生成150个结果。其中，148项在基于HDA的测定和参考方法之间一致。对两份具有未解析HDA检测结果的样品进行了重复检测，结果与参考方法一致。基于HDA的测定证明了对CYP 2C 9酶（CYP 2C 9 *2和CYP 2C 9 *3）的VKORC 1 - 1639 G>A SNP和两个SNP（430 C>T和1075 A>C）进行基因分型的临床可接受性能，所有这些均与华法林药物遗传学相关。
The response to the anticoagulant drug warfarin is greatly affected by genetic polymorphisms in the VKORC1 and CYP2C9 genes. Genotyping these polymorphisms has been shown to be important in reducing the time of the trial and error process for finding the maintenance dose of warfarin thus reducing the risk of adverse effects of the drug. We developed a real-time isothermal DNA amplification system for genotyping three single nucleotide polymorphisms (SNPs) that influence warfarin response. For each SNP, real-time isothermal Helicase Dependent Amplification (HDA) reactions were performed to amplify a DNA fragment containing the SNP. Amplicons were detected by fluorescently labeled allele specific probes during real-time HDA amplification. Fifty clinical samples were analyzed by the HDA-based method, generating a total of 150 results. Of these, 148 were consistent between the HDA-based assays and a reference method. The two samples with unresolved HDA-based test results were repeated and found to be consistent with the reference method. The HDA-based assays demonstrated a clinically acceptable performance for genotyping the VKORC1 -1639G>A SNP and two SNPs (430C>T and 1075A>C) for the CYP2C9 enzyme (CYP2C9*2 and CYP2C9*3), all of which are relevant in warfarin pharmacogenentics.
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影响因子：
6.5
作者：
Baglin, T. P.;Cousins, D.;Watson, H. G.
通讯作者：
Watson, H. G.
影响因子：
4
作者：
Linder, MW;Looney, S;Valdes, R
通讯作者：
Valdes, R
DOI：
10.1073/pnas.87.5.1874
发表时间：
1990-03-01
影响因子：
11.1
作者：
GUATELLI, JC;WHITFIELD, KM;GINGERAS, TR
通讯作者：
GINGERAS, TR
影响因子：
6.7
作者：
Scordo, MG;Pengo, V;Padrini, R
通讯作者：
Padrini, R
影响因子：
3.5
作者：
King, Cristi R.;Porche-Sorbet, Rhonda M.;Eby, Charles
通讯作者：
Eby, Charles