High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance Gene pfmdr1.
Polymorphisms were examined in 2 Plasmodium falciparum genes, as were chloroquine responses of clones and isolates from a village in eastern Sudan. There was a significant association between an allele of the P. falciparum chloroquine resistance transporter gene (pfcrt-T76) and both in vitro and in vivo resistance. There was a less significant association with the multidrug resistance gene pfmdr1-Y86 allele. A significant association between pfmdr1-Y86 and pfcrt-T76 was apparent among resistant isolates, which suggests a joint action of the 2 genes in high-level chloroquine resistance.
Babiker
H A
HA
Institute of Cell, Animal, and Population Biology, University of Edinburgh, Edinburgh, EH9 3JT, Scotland, United Kingdom. H.Babiker@ed.ac.uk
Pringle
S J
SJ
Abdel-Muhsin
A
A
Mackinnon
M
M
Hunt
P
P
Walliker
D
D
D018528:ATP-Binding Cassette Transporters; D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D002999:Clone Cells; D004351:Drug Resistance; D017125:Genes, Protozoan; D006801:Humans; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009154:Mutation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D013397:Sudan
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine