Short report: polymorphisms in the pfcrt and pfmdr1 genes of Plasmodium falciparum and in vitro susceptibility to amodiaquine and desethylamodiaquine.
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.
Echeverry
Diego F
DF
International Center for Medical Research and Training (CIDEIM), Cali, Valle, Colombia. difereg@cideim.org.co
Holmgren
Gabrielle
G
Murillo
Claribel
C
Higuita
Juan C
JC
Björkman
Anders
A
Gil
Jose P
JP
Osorio
Lyda
L
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*
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