title: Short communication: high prevalence of the cytochrome P450 2C8*2 mutation in Northern Ghana.
abstract: Recently, Ghana has changed the first-line treatment of uncomplicated malaria from chloroquine to amodiaquine (AQ) plus artesunate. AQ may cause adverse events such as agranulocytosis and hepatoxicity. The pro-drug AQ is transformed by cytochrome P450 CYP2C8 to the active metabolite N-desethylaminodiaquine. Several polymorphic variants of CYP2C8 are known, some with reduced activity. In 200 randomly selected children from Northern Ghana, we determined the allele frequencies of the CYP2C8 variants CYP2C8*1 (wild type), CYP2C8*2, CYP2C8*3, and CYP2C8*4. We did not detect CYP2C8*3 and CYP2C8*4, but CYP2C8*2 showed an allele frequency of 0.1675. AQ metabolism in patients with CYP2C8*2 may be impaired, and with an increase of AQ based treatment the risk of severe adverse events may mount.
authors.affiliation: Institute of Tropical Medicine, Charité-University Medicine Berlin, Berlin, Germany. susanne.roewer@charite.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Röwer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bienzle
authors.forename: Alexander
authors.initials: A
authors.lastname: Weise
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lambertz
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.forename: Rowland N
authors.initials: RN
authors.lastname: Otchwemah
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfützner
authors.forename: Frank P
authors.initials: FP
authors.lastname: Mockenhaupt
mesh_terms: D000655:Amodiaquine / Q000009:adverse effects / Q000627:therapeutic use; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use; D037621:Artemisinins / Q000627:therapeutic use; D000077332:Artesunate; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D065727:Cytochrome P-450 CYP2C8; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005869:Ghana; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D011355:Prodrugs / Q000009:adverse effects / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D011355:Prodrugs; D012717:Sesquiterpenes; D000655:Amodiaquine; D000077332:Artesunate; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8