Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea
- PMID:16506047
- PMCID: PMC4450653
- DOI: 10.1007/s00228-005-0092-9
Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea
Abstract
Objective: Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of artemisinin drugs, a novel series of antimalarials. Our aim was to analyze the prevalence of the most commonly observed CYP2B6 alleles in malaria-endemic populations of West Africa (WA) and Papua New Guinea (PNG).
Methods: Using a post-PCR ligation detection reaction-fluorescent microsphere assay, frequencies of CYP2B6*1A, *2, *3, *4, *5, *6, *7, and *9 were determined in WA (n=166) and PNG (n=174). To compare with the results of previous studies, we also determined the allele frequencies in 291 North Americans of various ethnic groups.
Results: Significant differences were observed between WA and PNG for the frequencies of alleles CYP2B6*1A (45% vs 33%, P = 0.003), *2 (4% vs. 0%, P<0.001), *6 (42% vs 62%, P<0.001), and *9 (8% vs 1%, P<0.001), and genotypes *1A/*9 (9% vs 0%, P<0.001) and *6/*6 (17% vs 43%, P<0.001). The frequencies of CYP2B6 genotypes in the populations were in Hardy-Weinberg equilibrium, except for PNG where an overall significant deficit of heterozygosity was observed (H (O)=0.431, H (E)=0.505, P=0.004). The allele frequencies in Asian-Americans and Caucasians-Americans were comparable to those documented for Japanese and Caucasian populations.
Conclusions: CYP2B6 variants, previously shown to affect metabolism of a variety of drugs, occur in WA and PNG, and there are significant genetic differences at the CYP2B6 locus in these populations. It may be important to determine if these differences alter the efficacy of artemisinin drugs.
References
- Erickson DA, Mather G, Trager WF, Levy RH, Keirns JJ. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999;27:1488–1495. - PubMed
- Ward BA, Gorski JC, Jones DR, Hall SD, Flockhart DA, Desta Z. The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther. 2003;306:287–300. - PubMed
- Li XQ, Bjorkman A, Andersson TB, Gustafsson LL, Masimirembwa CM. Identification of human cytochrome P(450)s that metabolise anti-parasitic drugs and predictions of in vivo drug hepatic clearance from in vitro data. Eur J Clin Pharmacol. 2003;59:429–442. - PubMed
- Simonsson US, Jansson B, Hai TN, Huong DX, Tybring G, Ashton M. Artemisinin autoinduction is caused by involvement of cytochrome P450 2B6 but not 2C9. Clin Pharmacol Ther. 2003;74:32–43. - PubMed
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