title: Absence of the human CYP2C8*3 allele in Ugandan children exposed to Plasmodium falciparum malaria.
abstract: Study of host pharmacogenetics can improve our knowledge of mechanisms of drug resistance selection and spread. This issue has recently been addressed with respect to chloroquine and amodiaquine in malaria endemic areas of West and East Africa. Here we report, from surveys performed in two different areas of Uganda, that the human CYP2C8*3 allele, which had been reported to be strongly associated with parasite drug resistance in Zanzibar, is absent, being a marker of genetic admixture of the Zanzibari population with a Caucasoid component. Moreover, a retrospective analysis of CYP2C8*2 and the Plasmodium falciparum drug resistant pfmdr1 86Y allele does not show any association, which may be related to the high level of drug resistance.
authors.affiliation: University of Botswana-University of Pennsylvania Partnership, Gaborone, Botswana; Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy. Electronic address: paganottig@botswana-upenn.co.bw.
authors.forename: Giacomo Maria
authors.initials: GM
authors.lastname: Paganotti
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cosentino
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Russo
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Tabacchi
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gramolelli
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Coluzzi
authors.affiliation: Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Romano
mesh_terms: D000483:Alleles; D002648:Child; D065727:Cytochrome P-450 CYP2C8 / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005787:Gene Frequency; D005798:Genes, Bacterial; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics* / Q000469:parasitology*; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D014454:Uganda
chemical_list: D065727:Cytochrome P-450 CYP2C8
keywords: CYP2C8; Malaria drug resistance; Pharmacogenetics; Plasmodium falciparum malaria; Uganda; pfmdr1