Pharmacogenetics of CYP2B6, CYP2A6 and UGT2B7 in HIV treatment in African populations: focus on efavirenz and nevirapine.
The CYP450 and UGT enzymes are involved in phase I and phase II metabolism of the majority of clinically prescribed drugs, including the non-nucleoside reverse transcriptase inhibitors, efavirenz and nevirapine, used in the treatment of HIV/AIDS. Variations in the activity of these enzymes due to gene polymorphisms can affect an individual's drug response or may lead to adverse drug reactions. There is an inter-ethnic distribution in the frequency of these polymorphisms, with African populations exhibiting higher genetic diversity compared to other populations. African specific alleles with clinical relevance have also emerged. Given the high prevalence of HIV/AIDS in sub-Saharan Africa, understanding the frequency of pharmacogenetically relevant alleles in populations of African origin, and their impact on efavirenz and nevirapine metabolism, is becoming increasingly critical. This review aims to investigate ethnic variation of CYP2B6, CYP2A6 and UGT2B7, and to understand the pharmacogenetic relevance when comparing frequencies in African populations to other populations worldwide.
Department of Biochemistry, Faculty of Natural and Agricultural SciencesSchool of Biological Science, University of Pretoria , Pretoria , South Africa and.
Antoinette
A
Čolić
Marco
M
Alessandrini
Michael S
MS
Pepper
D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D048588:Benzoxazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044383:Black People / Q000235:genetics*; D003521:Cyclopropanes; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics* / Q000378:metabolism; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics* / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D019829:Nevirapine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D019829:Nevirapine; C585710:CYP2A6 protein, human; C585599:CYP2B6 protein, human; D065637:Cytochrome P-450 CYP2A6; D065702:Cytochrome P-450 CYP2B6; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; C098320:efavirenz
Drug metabolism; HIV/AIDS; hepatotoxicity; inter-ethnic variability; neurotoxicity