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interethnic differences in genetic polymorphisms of cyp2d6 in the us population- clinical implications.doc

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Interethnic Differences in Genetic Polymorphisms of CYP2D6 in the US Population: Clinical Implications nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;nbsp;作者：Stephen Bernarda, Kathleen A. Nevilleb, Anne T. Nguyenb, David A. Flockhartb nbsp;【关键词】nbsp; CYP2D6,polymorphism,amp;#8226;,Hepatic,metabolism,amp;#8226;,5-HT3-receptor,antagonist,antiemetics,amp;#8226;,Genetic,variability 　　LEARNING OBJECTIVESnbsp; 　　After completing this course, the reader will be able to: 　　List the four different genotypes for CYP2D6 polymorphism. 　　Understand the potential effects of CYP2D6 polymorphism on the efficacy and safety for drugs metabolized via this enzyme. 　　List the ethnic groups that are most frequently affected by genetic variation of the CYP2D6 enzyme. 　　ABSTRACTnbsp; nbsp; 　　DNA polymorphisms have been identified in the genes encoding a number of the cytochrome P450 (CYP) enzymes, leading to wide interindividual variation in drug clearance. CYP2D6 metabolizes a significant number of clinically used medications, and genetic variants of the CYP2D6 isozyme that result in varying levels of metabolic activity are of clinical importance in some settings. The exact nature of the clinical effect caused by polymorphisms of the gene depends on the drug in question and the specific variant alleles expressed, as individual variants result in differing phenotypes with a range of levels of enzymatic activity. 　　Compromised drug efficacy due to CYP2D6 variation has been documented with a variety of agents, and this review considers a number of examples, including the 5-HT3-receptor antagonists, which are used in oncology supportive care for the prophylaxis of nausea and vomiting. CYP2D6 is involved in the metabolism of all of the most commonly available agents, except granisetron, and their efficacy and side effects may therefore be affected by the CYP2D6 polymorphism. 　　Significant interethnic differences in CYP2D6 allele frequencies have been dem