title: Short report: polymorphisms in the pfcrt and pfmdr1 genes of Plasmodium falciparum and in vitro susceptibility to amodiaquine and desethylamodiaquine.
abstract: The potential role of polymorphisms in the pfcrt and pfmdr1 genes and in vitro susceptibility to amodiaquine and desethylamodiaquine were explored in 15 chloroquine-resistant Colombian Plasmodium falciparum isolates. Single nucleotide polymorphisms in the pfcrt gene, including a newly reported mutation (S334N), were seen in isolates with decreased susceptibility to amodiaquine and desethylamodiaquine. The lowest susceptibility found to amodiaquine was observed in an isolate carrying a pfcrt and pfmdr1 Dd2-like haplotype, whereas a pfcrt haplotype related to the 7G8 Brazilian strain was found in a Colombian isolate with the lowest susceptibility to desethylamodiaquine. This exploratory study suggests that polymorphisms in the pfcrt and pfmdr1 genes play a role in amodiaquine and desethylamodiaquine resistance and warrants further study.
authors.affiliation: International Center for Medical Research and Training (CIDEIM), Cali, Valle, Colombia. difereg@cideim.org.co
authors.forename: Diego F
authors.initials: DF
authors.lastname: Echeverry
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Holmgren
authors.forename: Claribel
authors.initials: C
authors.lastname: Murillo
authors.forename: Juan C
authors.initials: JC
authors.lastname: Higuita
authors.forename: Anders
authors.initials: A
authors.lastname: Björkman
authors.forename: Jose P
authors.initials: JP
authors.lastname: Gil
authors.forename: Lyda
authors.initials: L
authors.lastname: Osorio
mesh_terms: D000595:Amino Acid Sequence; D000655:Amodiaquine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001483:Base Sequence; D003105:Colombia; D004351:Drug Resistance / Q000235:genetics*; D020128:Inhibitory Concentration 50; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C047386:desethylamodiaquine