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[全基因组关联研究在个性化医疗建立中的挑战:聚焦华法林和卡马西平的药物基因组学]

[Challenge in genome-wide association study for establishment of personalized medicine: focusing on the pharmacogenomics of warfarin and carbamazepine].

作者信息

Mushiroda Taisei

机构信息

RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.

出版信息

Rinsho Byori. 2013 May;61(5):422-7.

Abstract

Drug efficacies and adverse drug reactions(ADRs) are often unpredictable, owing to the fact that responses to drugs vary among different individuals; however, it is believed that applying knowledge of pharmacogenomics (PGx) in clinical treatment can help to improve the prediction of drug responses, leading to the establishment of personalized medicine that aims to provide the right drug at the appropriate dose for each individual patient. In recent years, the FDA has recommended the genotyping of polymorphisms in drug-metabolizing enzymes and HLA prior to drug administration to avoid severe ADRs to many drugs, such as carbamazepine and abacavir. A genome-wide association study (GWAS) is useful to identify genomic biomarkers that can predict the efficacy or risk of ADRs to various drugs. In order to apply genomic biomarkers to clinical therapeutics, prospective clinical trials will be necessary to evaluate an intervention based on genetic tests.

摘要

药物疗效和药物不良反应(ADR)往往不可预测,因为不同个体对药物的反应存在差异;然而,人们认为在临床治疗中应用药物基因组学(PGx)知识有助于提高对药物反应的预测,从而建立个性化医疗,旨在为每位患者提供合适剂量的正确药物。近年来,美国食品药品监督管理局(FDA)建议在给药前对药物代谢酶和人类白细胞抗原(HLA)中的多态性进行基因分型,以避免对许多药物,如卡马西平和阿巴卡韦产生严重的药物不良反应。全基因组关联研究(GWAS)有助于识别可预测各种药物疗效或药物不良反应风险的基因组生物标志物。为了将基因组生物标志物应用于临床治疗,有必要进行前瞻性临床试验,以评估基于基因检测的干预措施。

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