Pharmacogenetics in Africa, an Opportunity for Appropriate Drug Dosage Regimens: on the Road to Personalized Healthcare

Approximately 60 years ago, the metabolism and disposition of isoniazid, an antituberculosis drug, was one of the earliest demonstrations of pharmacogenetic differences in drug handling that resulted in clinical consequences.2 There were marked differences in excretion of the drug among individuals who were then classified into slow acetylators (SA) and rapid acetylators of isoniazid with SA individuals being more prone to suffer from isoniazid-induced peripheral neuropathy. After the cytosolic enzyme, N-acetyltransferase 2 was cloned, many genetic variants were found that explained the rapid acetylators and SA status, and epidemiological studies showed that the SA status could vary from 5 to 95% depending on the population studied.2 Since the discovery of differences in extent of excretion of isoniazid, a vast literature has developed documenting many other genetic polymorphisms for drug metabolizing enzymes and drug transporters. Many of these genetic polymorphisms are known to have clinical effects and to exhibit interethnic differences (Table 1). Studies are now including pharmacogenetic variables in optimizing the clinical use of some drugs; for example, Azuma et al.3 recently conducted a randomized controlled trial for pharmacogenetics-based therapy and showed that a NAT-2 genotype–guided regimen reduces isoniazid-induced liver injury and early treatment failure in tuberculosis patients. To ensure translation of research to the bedside, the Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network is working to establish guidelines for clinical use of pharmacogenetic data.4 The clinical importance of pharmacogenetic traits has made major drug regulatory agencies such as the US Food and Drug Administration and the European Medicines Agency develop policy documents and guidelines on the subject that can be found through a search of their world-wide websites. The pharmaceutical industry has also formed the Industry-Pharmacogenomics Working Group (www.i-pwg. org) to work on research and ethical guidelines on the integration of pharmacogenetics in drug discovery, development, and clinical use of medicines. Many drugs now carry pharmacogenetics information in their labels or leaflets, and the US Food and Drug Administration has since approved a number of pharmacogenetics tests that could be used to improve the use of these drugs (www.pharmgkb.org).