DMET™ Microarray Technology for Pharmacogenomics-Based Personalized Medicine
DMET™ Microarray Technology for Pharmacogenomics-Based Personalized Medicine
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DOI：
10.1007/978-1-60761-663-4_7
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Mansfield, Elaine
中科院分区：
文献类型：
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作者：
Burmester, James K.;Sedova, Marina;Mansfield, Elaine
单核苷酸多态性（SNP）形式的人类基因组序列变异以及更复杂的结构变异（如插入、复制和缺失）是每个个体对药物反应的基础，因此可能会出现药物不良反应。药物遗传学领域的持续挑战是进一步理解遗传变异和差异药物反应之间的关系，其总体目标是这将导致药物安全性和有效性的改善。Affytek（R）DMET（TM）Plus Premier Pack（DMET代表药物代谢酶和转运蛋白）能够在单个阵列上对吸收、分布、代谢和消除（ADME）相关基因中的已知多态性进行高度多重的基因分型。DMET Plus Panel检测了225个基因中的标记物，这些标记物在I期和II期药物代谢酶以及药物转运蛋白中具有记录的功能意义。DMET检测试剂盒的功效先前已在几种不同药物（包括华法林和氯吡格雷）中得到证实。在一项使用早期四色版本的检测方法的研究中，证明华法林剂量可能受到细胞色素P450（CYP450）4F2变体的影响。此外，该试验已用于证明酶活性降低的CYP2C19变体导致活性氯吡格雷代谢物水平降低，导致血小板抑制降低，与DNA变体非携带者相比，心血管事件发生率更高。因此，高度多重SNP基因分型集中在ADME相关的多态性，应该能够研究开发更安全的药物，具有更大的疗效。
Human genome sequence variation in the form of single nucleotide polymorphisms (SNPs) as well as more complex structural variation such as insertions, duplications, and deletions underlies each individual's response to drugs and thus the likelihood of experiencing an adverse drug reaction. The ongoing challenge of the field of pharmacogenetics is to further understand the relationship between genetic variation and differential drug responses, with-the overarching goal being that this will lead to improvements in both the safety and efficacy of drugs. The Affymetrix (R) DMET (TM) Plus Premier Pack (DMET stands for Drug Metabolizing Enzymes and Transporters) enables highly multiplexed genotyping of known polymorphisms in Absorption, Distribution, Metabolism, and Elimination (ADME)-related genes on a single array. The DMET Plus Panel interrogates markers in 225 genes that have documented functional significance in phase I and phase II drug metabolism enzymes as well as drug transporters. The power of the DMET Assay has previously been demonstrated with regard to several different drugs including warfarin and clopidogrel. In a research study using an earlier four-color version of the assay, it was demonstrated that warfarin dosing can be influenced by a cytochrome P450 (CYP) 4F2 variant. Additionally, the assay has been used to demonstrate that CYP2C19 variants with decreased enzyme activity led to lower levels of the active clopidogrel metabolite, resulting in a decreased inhibition of platelets and a higher rate of cardiovascular events when compared to noncarriers of the DNA variant. Thus, highly multiplexed SNP genotyping focused on ADME-related polymorphisms should enable research into development of safer drugs with greater efficacy.