Association of Plasmodium falciparum chloroquine resistance transporter variant T76 with age-related plasma chloroquine levels.
The mutation leading to the substitution of a threonine (T76) for a lysine at position 76 of the Plasmodium falciparum chloroquine resistance transporter (PfCRT) was genotyped in 100 Nigerian children with asymptomatic parasitemia. Isolates containing both pfcrt variants were found to harbor higher numbers of parasite clones (P < 0.002). The prevalence of the pfcrt T76 variant decreased with age (P < 0.0001) and increased with blood levels of chloroquine (CQ) (P < 0.0001). Whereas the K76 allele was more frequent in individuals without detectable plasma CQ levels (79.7%), only the pfcrt T76 variant was observed in children with CQ levels > 150 nmol/L. In individuals without detectable plasma CQ, the proportion of those with pfcrt T76 decreased from 60% in children < 2 years old to 23.5% in children > or = 6 years old (P < 0.01). The association of actual blood levels of CQ and the occurrence of pfcrt T76 underlines that the pfcrt T76 variant is in fact the mediator of CQ resistance.
May
Jürgen
J
Department of Molecular Medicine, Bernhard-Nocht-Institute for Tropical Medicine Hamburg, Germany. may@bni.uni-hamburg.de
Meyer
Christian G
CG
D000367:Age Factors; D000818:Animals; D000962:Antimalarials / Q000097:blood / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000097:blood / Q000627:therapeutic use*; D017931:DNA Primers; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology* / Q000469:parasitology; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009549:Nigeria / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D015800:Protozoan Proteins
D000962:Antimalarials; D017931:DNA Primers; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine