title: Prevalence of Plasmodium falciparum pfcrt polymorphisms and in vitro chloroquine sensitivity in Senegal.
abstract: Mutations in pfcrt K76T are associated with chloroquine resistance in Plasmodium falciparum. Previous studies of K76T mutations in Senegal reported the association of T76 with in vitro-resistant isolates, but this mutation was also prevalent in chloroquine-sensitive isolates. This suggests involvement of additional genetic loci in modulating chloroquine resistance. Additional pfcrt polymorphisms at codons A220S, Q271E, N326S and R371I have been found in chloroquine-resistant isolates. We wanted to test if sequential acquisition of mutations at these codons leads to in vitro chloroquine resistance. Stepwise accumulation of mutations was not detected, rather there was almost complete linkage between the pfcrt K76T mutation and polymorphisms in these codons. Therefore these additional polymorphisms do not enhance the correlation between pfcrt T76 and chloroquine resistance in Senegal. These data suggest that in vitro chloroquine resistance requires the genetic background of the pfcrt K76T mutation and additional mutations in genetic loci outside the pfcrt gene.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA. jdaily@partners.org
authors.forename: J P
authors.initials: JP
authors.lastname: Daily
authors.forename: C
authors.initials: C
authors.lastname: Roberts
authors.forename: S M
authors.initials: SM
authors.lastname: Thomas
authors.forename: O
authors.initials: O
authors.lastname: Ndir
authors.forename: T
authors.initials: T
authors.lastname: Dieng
authors.forename: S
authors.initials: S
authors.lastname: Mboup
authors.forename: D F
authors.initials: DF
authors.lastname: Wirth
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D017125:Genes, Protozoan / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D015800:Protozoan Proteins; D012675:Senegal / Q000453:epidemiology
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine