Журнал гликомики и липидомики
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Pharmacogenomics-guided approach to minimize adverse drug reactions

Shu-Feng Zhou

Adverse drug reactions (ADRs) are one of the major causes of patient morbidity and mortality. Pharmacogenetics is the study of how the genetic variations affect drug response in individual patients, while pharmacogenomics emphasizes the identification of the network of genes that govern drug response in individual patients using genome-wide approaches. Numerous genes, in particular those encoding drug metabolizing enzymes, drug transporters and drug targets, have been identified to affect drug response and ADRs. In the past decade, my laboratory has investigated the impact of polymorphisms of a number of important genes including CYP2B6, CYP2C9, ApoE, PXR/NR1I2, UGT1A1, GSTM1, GSTT1, GSTP1, TPMT, etc. on drug clearance, response, or ADRs. Mutations of these genes can significantly alter drug clearance, response or ADRs in different ethnic groups. In addition, mutations of certain genes can precipitate ADRs. Over the past years, genome-wide association studies (GWAS) have identified a number of common and rare variants that are associated with increased risk of ADRs. As affordable and reliable genetic testing tools become available to physicians, pharmacogenomics looks promising to facilitate individualization of drug therapy and as a result, this will maximize the therapeutic efficacy of drugs in patients while minimizing the occurrence of ADRs