Pharmacogenetics and adverse drug reactions

The rapidly expanding discipline of pharmacogenetics has helped to explain the mechanisms of susceptibility to several adverse drug reactions. The molecular details of the 'classical' adverse reactions, including malignant hyperthermia, haemolysis in patients with glucose-6-phosphatase deficiency, and acute porphyrias, have become clearer. In addition, associations have emerged between adverse reactions and various polymorphisms that affect drug action. Examples include associations between the human leucocyte-associated antigen HLA B*5701 and hypersensitivity reactions to flucloxacillin and to the HIV protease inhibitor abacavir; between HLA B*1502 and toxic epidermal necrolysis induced in Han Chinese by antiepileptic drugs; between ion-channel mutations and drug-induced torsade de pointes; and between alterations in mitochondrial DNA and several rare adverse effects. The task of identifying individuals susceptible to adverse drug reactions should gradually become easier as more pharmacogenetic associations are described. © 2010 Lippincott Williams & Wilkins.