CYP2C8 polymorphism frequencies among malaria patients in Zanzibar.
OBJECTIVE
The determination of the prevalence of the CYP2C8 main alleles in a typical set of malaria patients in Zanzibar, as these patients represent a typical population exposed to amodiaquine, an antimalarial mainly metabolized by CYP2C8. Also, to determine for the first time the frequencies of CYP2C8 alleles in native African populations.


METHODS
Polymerase chain reaction-restriction fragment polymorphism for the identification of CYP2C8*1, CYP2C8*2, CYP2C8*3 and CYP2C8*4 on a random population of 165 unrelated malaria patients.


RESULTS
The allele frequencies found were: CYP2C8*1 (wild type, 83.4%), CYP2C8*2 (13.9%), CYP2C8*3 (2.1%) and CYP2C8*4 (0.6%). In terms of genotypes, 70.4% of the patients showed the CYP2C8*1/ CYP2C8*1 genotypes, while heterozygous between the wild type and other minor alleles were seen in 26.0%. Finally, 3.6% of the patients were homozygous for slow metabolizer alleles. The frequencies observed are equivalent to those documented for African-Americans.


CONCLUSIONS
CYP2C8 non-wild type alleles have a significant prevalence in the East African population studied. The consequent frequency of 3.6% of patients homozygous for slow metabolizer alleles represent a significant fraction of the population potentially in higher risk of adverse effects due to a less efficient metabolism of amodiaquine. As approximately 10(6) first-line treatments are currently performed in Zanzibar per year, this represents a non-negligible absolute number of amodiaquine exposures. This information constitutes a background for the pharmacovigilance programs presently being employed in Zanzibar.
Cavaco
I
I
Centre for Molecular and Structural Biomedicine, Universidade do Algarve, Campus de Gambelas, Faro, 8000-117, Portugal.
Strömberg-Nörklit
J
J
Kaneko
A
A
Msellem
M I
MI
Dahoma
M
M
Ribeiro
V L
VL
Bjorkman
A
A
Gil
J P
JP
D000483:Alleles; D000655:Amodiaquine / Q000378:metabolism* / Q000627:therapeutic use; D000962:Antimalarials / Q000378:metabolism* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002675:Child, Preschool; D065727:Cytochrome P-450 CYP2C8; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D015995:Prevalence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013636:Tanzania
D000962:Antimalarials; D000655:Amodiaquine; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8