Genetic polymorphism of drug metabolising enzymes in African populations: implications for the use of neuroleptics and antidepressants.
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.
Masimirembwa
C M
CM
Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
Hasler
J A
JA
D000349:Africa; D000483:Alleles; D000928:Antidepressive Agents / Q000493:pharmacokinetics*; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases; D044383:Black People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D013379:Substrate Specificity
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6