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治疗学的药物遗传学方法。

Pharmacogenetics approach to therapeutics.

作者信息

Koo Seok Hwee, Lee Edmund Jon Deoon

机构信息

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

出版信息

Clin Exp Pharmacol Physiol. 2006 May-Jun;33(5-6):525-32. doi: 10.1111/j.1440-1681.2006.04402.x.

Abstract
  1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.
摘要
  1. 药物遗传学是指对药物反应中基因控制的变异进行研究。已知编码药物代谢酶、转运体、离子通道和药物受体的基因中的单核苷酸多态性(SNP)所引起的功能性变异与个体间和种族间的药物反应差异有关。这些基因中的遗传变异在影响药物疗效和毒性方面发挥作用。2. 快速、精确且具有成本效益的高通量技术平台对于对参与药物治疗可变反应病因的遗传标记进行大规模突变分析至关重要。3. 由于各种限制,如技术可及性有限、知识不足、变异体作用不明确以及伦理问题等,目前在一般临床实践中应用药物遗传学方法进行治疗仍远未实现。4. 药物作用由编码参与各种生化途径的不同蛋白质的多个基因之间的相互作用决定。随着快速涌现的SNP发现技术平台以及对SNP在疾病易感性和药物反应变异性中作用的广泛了解,预计在不久的将来药物遗传学治疗方法将得以兴起。这将对医疗保健产生深远的临床、经济和社会影响。

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