药物遗传学药物基因组学与个体化医学.pdf

第四章 药物遗传学、药物基因组学与 个体化医学 – 药物代谢与遗传因素 – 遗传多态性与药物代谢及分布 – SNP、基因芯片与药物基因组学 Patient Response to Medicine Varies “One size fits all ?!” “I have hypertension which is not being controlled. My doctor prescribes a drug for hypertension, we wait 3-4 months to find it’s not working and then try another one. In 18 months, I’ve tried 6 new medications and I’m fast losing confidence in this hit or miss approach and in my physician”. 药物遗传学(pharmacogenetics) • 一门由药理学和遗传学相互渗透而形成的以研究 人体对药物反应的的边缘学科。 • An ultimate goal of pharmacogenetics is to understand how someones genetic make-up determines how well a medicine works in his or her body, as well as what side effects are likely to occur. In 1902, British physician Sir Garrod A. suggested that genetic factors direct chemical transformations in humans and underlie individual variability. In 1957, Motulsky A.demonstrated the relationship between adverse drug reactions and genetically determined variation. Gurwitz D, Motulsky AG. “Drug reactions, enzymes, and biochemical genetics”: 50 years later. Pharmacogenomics. 2007;8(11):1479-84. Vogel F. coined the term pharmacogenetics in 1959 Kalow W.(1962) showed that an abnormal form of serum cholinesterase leads to catastrophic adverse reactions to succinylcholine (Anectine, Quelicin), and he wrote the first systematic account of pharmacogenetics. Audience:The Pharmacogenomics Journal is essential reading for geneticists, molecular biologists, clinical and molecular pharmacologists, as well as those working in biotechnology, drug discovery and drug development. 2001年，著名的 《Nature》杂志社创立 《Pharmacogenomics