Analysis of Sepik populations of Papua New Guinea suggests an increase of CYP2C19 null allele frequencies during the colonization of Melanesia.
The cytochrome P450 (CYP) isozyme CYP2C19 metabolizes clinically important drugs, including the anti-malarial proguanil currently used for multi-drug resistant Plasmodium falciparum malaria. CYP2C19 activity varies among geographical regions due to high frequencies of two null alleles (CYP2C19*2/*3) in Asian and especially Pacific populations. Previously, we reported an unprecedentedly high frequency of CYP2C19 poor metabolizers (PM) within populations of Vanuatu, which suggested even higher PM frequencies in Papua New Guinea. We examined CYP2C19 allele frequencies of three malarious populations from inland East Sepik Province, Papua New Guinea to evaluate this prediction and the use of proguanil in malaria treatment programs. These Papua New Guinean populations have PM frequencies intermediate between island South-east Asia and Vanuatu, most likely resulting from genetic drift during the settlement of the Pacific. This study highlights the medical consequences of population origins and the need for a better understanding of the genetic diversity of our global species.
Masta
Andrew
A
School of Medicine and Health Sciences, University of Papua New Guinea, Port Moresby, Papua New Guinea.
Lum
J Koji
JK
Tsukahara
Takahiro
T
Hwaihwanje
Ilomo
I
Kaneko
Akira
A
Paniu
Michael M
MM
Sapuri
Mathias
M
Takahashi
Nobuyuki
N
Ishizaki
Takashi
T
Kobayakawa
Takatoshi
T
Hombhanje
Francis W
FW
D000293:Adolescent; D000483:Alleles; D000962:Antimalarials / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005787:Gene Frequency; D040961:Genetic Drift; D014644:Genetic Variation; D005828:Genetics, Population; D006579:Heterozygote; D006801:Humans; D008297:Male; D008542:Melanesia; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D010219:Papua New Guinea; D002727:Proguanil / Q000378:metabolism
D000962:Antimalarials; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D002727:Proguanil