Chloroquine resistance in Plasmodium falciparum and polymorphism of the CG2 gene.
A distinct genotype (designated Dd2-type profile) consisting of 12 point mutations and 3 repetitive regions of the CG2 gene, a candidate gene for chloroquine resistance, has been associated with in vitro resistance in laboratory-adapted strains of Plasmodium falciparum. The DNA sequence of clinical isolates, characterized by in vitro and in vivo tests, was analyzed to evaluate whether the genotype corresponds to the phenotype in naturally occurring parasites. Eight of 11 chloroquine-resistant isolates had the Dd2 genotype. One resistant isolate (by in vitro assay) with a sensitive CG2 genotype was sensitive in vivo. Two resistant isolates and 6 sensitive isolates were multiple infections with mixed alleles. No typical CG2 genotype was found corresponding to the chloroquine-sensitive isolates. These results suggest a strong association between the drug-resistant and CG2 genotypes and support the hypothesis that the CG2 gene may be implicated in chloroquine resistance.
Basco
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LK
Institut de Recherche pour le Développement, Laboratoire de Recherche sur le Paludisme, Laboratoire Associé Francophone 302, Organisation de Coordination pour la Lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon. oceac@camnet.cm
Ringwald
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P
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA
D000954:Antigens, Surface; D000962:Antimalarials; C109422:CG2 protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine