Performance of commercial platforms for rapid genotyping of polymorphisms affecting warfarin dose
Performance of commercial platforms for rapid genotyping of polymorphisms affecting warfarin dose
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DOI：
10.1309/1e34uapr06pj6hml
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发表时间：
2008-06-01
影响因子：
3.5
通讯作者：
Eby, Charles
中科院分区：
文献类型：
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作者：
King, Cristi R.;Porche-Sorbet, Rhonda M.;Eby, Charles
由于华法林治疗窗狭窄且治疗剂量不可预测，因此开始华法林治疗与出血相关。基于药物遗传学的给药算法可以提高华法林初始给药的准确性，但需要对细胞色素P-450 2C 9（CYP 20）*2和 *3单核苷酸多态性（SNP）和维生素K环氧化物还原酶（VKORC 1）SNP进行快速基因分型。我们评价了4种商业系统：INFINITI分析仪（AutoGenomics，卡尔斯巴德，CA）、Invader测定（Third Wave Technologies，麦迪逊，WI）、Tag-It突变检测测定（Luminex Molecular Diagnostics，前身为Tm Bioscience，多伦多，加拿大）和焦磷酸测序（Biotage，乌普萨拉，瑞典）。我们对112份DNA样本进行了基因分型，并通过双向测序解决了任何差异。INFINITI分析仪对所有SNP的准确率为100%，需要8小时。Invader和Tag-It对于CYP 2C 9 SNP是100%准确的，对于VKORC 1 - 163913673 SNP是99%准确的，并且分别需要3小时和8小时。焦磷酸测序对CYP 2C 9 *2的准确度为99%，对CYP 2C 9 *3的准确度为100%，对VKORC I的准确度为100%，需要4小时。目前的商业平台提供了准确和快速的基因型药物遗传学剂量在开始华法林治疗。
Initiation of warfarin therapy is associated with bleeding owing to its narrow therapeutic window and unpredictable therapeutic dose. Pharmacogenetic-based dosing algorithms can improve accuracy of initial warfarin dosing but require rapid genotyping for cytochrome P-450 2C9 (CYP20) *2 and *3 single nucleotide polymorphisms (SNPs) and a vitamin K epoxide reductase (VKORC1) SNP. We evaluated 4 commercial systems: INFINITI analyzer (AutoGenomics, Carlsbad, CA), Invader assay (Third Wave Technologies, Madison, WI), Tag-It Mutation Detection assay (Luminex Molecular Diagnostics, formerly Tm Bioscience, Toronto, Canada), and pyrosequencing (Biotage, Uppsala, Sweden). We genotyped 112 DNA samples and resolved any discrepancies with bidirectional sequencing.The INFINITI analyzer was 100% accurate for all SNPs and required 8 hours. Invader and Tag-It were 100% accurate for CYP2C9 SNPs, 99% accurate for VKORC 1 -163913673 SNP, and required 3 hours and 8 hours, respectively. Pyrosequencing was 99% accurate for CYP2C9 *2, 100% accurate for CYP2C9 *3, and 100% accurate for VKORC I and required 4 hours. Current commercial platforms provide accurate and rapid genotypes for pharmacogenetic dosing during initiation of warfarin therapy.