8张咸宁-Phmarcogenetics.pptVIP

Pharmacogenetics and Pharmacogenomics ZHANG Xian-Ning, PhD zhangxianning@ Tel Office: C303, Teaching Building 2014/10 Learning Objectives What is pharmacogenetics? What is the ultimate goal of pharmacogenetics? What is pharmacogenomics ? What is the ultimate goal of pharmacogenomics? Patient Response to Medicine Varies “One size fits all ?!” Pharmacogenetics Pharmacogenetics is the study of interindividual variations in DNA sequence related to drug response. 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血清胆碱酯酶 leads to catastrophic adverse reactions to succinylcholine琥珀胆碱 (Anectine, Quelicin), and he wrote the first systematic account of pharmacogenetics. Pharmacogenomics Pharmacogenomics is the study of the variability of the expression of individual genes relevant to disease susceptibility as well as drug response at cellular, tissue, individual or population level. The term is broadly applicable to drug design, discovery, and clinical development. The ultimate goal of pharmacogenomics A. Better, Safer Drugs the First Time B. More Accurate Methods of Determining Appropriate Drug Dosages C. Advanced Screening for Disease Conservation vs. Variation Pharmacogenetics Genetic Polymorphism: common variation in DNA sequence (i.e. in 1% of popu