Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea.
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.
Mehlotra
Rajeev K
RK
Center for Global Health and Diseases, School of Medicine, Case Western Reserve University, Wolstein Research Building #4204, Cleveland, OH 44106-7286, USA. rkm@case.edu
Ziats
Mark N
MN
Bockarie
Moses J
MJ
Zimmerman
Peter A
PA
D000349:Africa / Q000453:epidemiology; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065702:Cytochrome P-450 CYP2B6; D019353:Endemic Diseases; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity; D008288:Malaria / Q000453:epidemiology* / Q000235:genetics; D017720:Molecular Epidemiology; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D010219:Papua New Guinea / Q000453:epidemiology; D010597:Pharmacogenetics; D015995:Prevalence
D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating