title: Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands.
abstract: Amodiaquine (AQ) is a 4-aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short-lived quinine-imine. To complete the genetic variation picture of the main genes involved in AQ metabolism in the Zanzibar population, previously characterised for CYP2C8, we analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately 27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low incidence of fast metabolisers, revealing a relatively safe genetic background in Zanzibar's population regarding the appearance of adverse effects.
authors.affiliation: Institute of Biotechnology and Bioengineering, Center of Molecular and Structural Biomedicine, University of Algarve, Faro, Portugal. isacavaco@ualg.pt
authors.forename: I
authors.initials: I
authors.lastname: Cavaco
authors.forename: R
authors.initials: R
authors.lastname: Piedade
authors.forename: M I
authors.initials: MI
authors.lastname: Msellem
authors.forename: A
authors.initials: A
authors.lastname: Bjorkman
authors.forename: J P
authors.initials: JP
authors.lastname: Gil
mesh_terms: D000483:Alleles; D000634:Aminoquinolines / Q000378:metabolism* / Q000627:therapeutic use; D000962:Antimalarials / Q000378:metabolism* / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005843:Geography; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D013636:Tanzania; D055815:Young Adult
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C001920:4-aminoquinoline