Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea
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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).
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.
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.
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.
KeywordsArtemisinin CYP2B6 alleles Malaria Papua New Guinea West Africa
We are thankful to Dr. Charles King, Dr. Keith Armitage, Dr. Carolyn Myers, Dr. Mohammed Orloff, Mr. David McNamara, and Mr. Shannon Bruse for their comments on the manuscript. This work was supported by a grant (AI-52312) from National Institutes of Health to P.A.Z. R.K.M. was supported by Fogarty International Center and in part by a grant (AI-36478) from National Institutes of Health. The experiments comply with the current laws, inclusive of ethics approval, of the United States of America.
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