Analysis of the key pfcrt point mutation and in vitro and in vivo response to chloroquine in Yaoundé, Cameroon.
The putative key codon (Lys-76 in sensitive parasites and Thr-76 in resistant parasites) of the novel candidate gene for chloroquine resistance, Plasmodium falciparum chloroquine resistance transporter (pfcrt), was determined by polymerase chain reaction-restriction fragment length polymorphism from 111 Cameroonian isolates and was compared with in vivo and in vitro responses to chloroquine. The key codon was significantly associated (P< .001) with responses in vivo (92% sensitivity and 76% specificity) and in vitro (97% sensitivity and 81% specificity). Some discordant results were due to multiclonal infections. The high, but not perfect, correlation between the pfcrt polymorphism and the phenotype implies that a single point mutation in codon 76 of the pfcrt gene is the major, but possibly not the sole, determinant for chloroquine resistance.
Basco
L K
LK
Unité de Recherche Paludologie Afro-Tropicale, Institut de Recherche pour le Développement, and Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la Lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon.
Ringwald
P
P
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002163:Cameroon; D002648:Child; D002738:Chloroquine / Q000494:pharmacology*; D003062:Codon; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D010641:Phenotype; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins; D012680:Sensitivity and Specificity
D000962:Antimalarials; D003062:Codon; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine