Genetic Polymorphism of Drug Metabolising Enzymes in African Populations: Implications for the Use of Neuroleptics and Antidepressants

• Published in: Brain Research Bulletin Vol. 44; no. 5; pp. 561 - 571
• Main Authors: Masimirembwa, Collen M., Hasler, Julia A.
• Format: Book Review Journal Article
• Language: English
• Published: United States Elsevier Inc 1997
• Subjects: Africa; African Continental Ancestry Group - genetics; Alleles; Antidepressive Agents - pharmacokinetics; Antipsychotic Agents - pharmacokinetics; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P-450 CYP2D6 - metabolism; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; Genetic Variation; Humans; Interindividual and interethnic variation; Mixed Function Oxygenases - genetics; Mixed Function Oxygenases - metabolism; Polymorphism, Genetic; Polymorphisms in Africa; Psychoactive drugs; Substrate Specificity; Polymorphisms in Africa; Interindividual and interethnic variation; Psychoactive drugs; Cytochrome P450
• DOI: 10.1016/S0361-9230(97)00307-9
• ISSN: 0361-9230

Metabolism of most drugs influences their pharmacological and toxicological effects. Drugs particularly affected are those with a narrow therapeutic window and that are subjected to considerable first-pass metabolism. Much of the interindividual and interethnic differences in effects of drugs is now attributable to genetic differences in their metabolism. Genetic polymorphisms have been described for many drug-metabolising enzymes in Caucasian and Oriental populations, the most well-characterised being those for cytochrome P450 2D6, cytochrome P450 2C19, glutathione S-transferases, and N-acetyl transferase 2. African populations have been studied to a lesser extent, but it is apparent that populations within Africa are heterogeneous with respect to these polymorphisms. In addition, although some allelic variants are common to all populations throughout the world (e.g., CYP2D6∗5 ), some allelic variants are specific for an African population (e.g., CYP2D6∗17 ). The polymorphisms give rise to enzymes with changed or no activity towards drug substrates. Two of the most important enzymes for metabolism of neuroleptics and other psychoactive drugs are CYP2D6 and CYP2C19. This article compares the current information on polymorphisms of these two enzymes in African and other populations and discusses the implications of these polymorphisms for neuropharmacotherapy.