title: In vitro susceptibility to quinine and microsatellite variations of the Plasmodium falciparum Na+/H+ exchanger (Pfnhe-1) gene: the absence of association in clinical isolates from the Republic of Congo.
abstract: BACKGROUND
  Quinine is still recommended as an effective therapy for severe cases of Plasmodium falciparum malaria, but the parasite has developed resistance to the drug in some cases. Investigations into the genetic basis for quinine resistance (QNR) suggest that QNR is complex and involves several genes, with either an additive or a pairwise effect. The results obtained when assessing one of these genes, the plasmodial Na+/H+ exchanger, Pfnhe-1, were found to depend upon the geographic origin of the parasite strain. Most of the associations identified have been made in Asian strains; in contrast, in African strains, the influence of Pfnhe on QNR is not apparent. However, a recent study carried out in Kenya did show a significant association between a Pfnhe polymorphism and QNR. As genetic differences may exist across the African continent, more field data are needed to determine if this association exists in other African regions. In the present study, association between Pfnhe and QNR is investigated in a series of isolates from central Africa.
  
  
  METHODS
  The sequence analysis of the polymorphisms at the Pfnhe-1 ms4760 microsatellite and the evaluation of in vitro quinine susceptibility (by isotopic assay) were conducted in 74 P. falciparum isolates from the Republic of Congo.
  
  
  RESULTS
  Polymorphisms in the number of DNNND or NHNDNHNNDDD repeats in the Pfnhe-1 ms4760 microsatellite were not associated with quinine susceptibility.
  
  
  CONCLUSIONS
  The polymorphism in the microsatellite ms4760 in Pfnhe-1 that cannot be used to monitor quinine response in the regions of the Republic of Congo, where the isolates came from. This finding suggests that there exists a genetic background associated with geographic area for the association that will prevent the use of Pfnhe as a molecular marker for QNR. The contribution of Pfnhe to the in vitro response to quinine remains to be assessed in other regions, including in countries with different levels of drug pressure.
authors.affiliation: Unité de Parasitologie, Unité Mixte de Recherche 6236, Institut de Recherche Biomédicale des Armées-Antenne de Marseille, Marseille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Briolant
authors.forename: Stéphane
authors.initials: S
authors.lastname: Pelleau
authors.forename: Hervé
authors.initials: H
authors.lastname: Bogreau
authors.forename: Philippe
authors.initials: P
authors.lastname: Hovette
authors.forename: Agnès
authors.initials: A
authors.lastname: Zettor
authors.forename: Jacky
authors.initials: J
authors.lastname: Castello
authors.forename: Eric
authors.initials: E
authors.lastname: Baret
authors.forename: Rémy
authors.initials: R
authors.lastname: Amalvict
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.forename: Bruno
authors.initials: B
authors.lastname: Pradines
mesh_terms: D000595:Amino Acid Sequence; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D003223:Congo / Q000453:epidemiology; D004351:Drug Resistance; D005838:Genotype; D006801:Humans; D020128:Inhibitory Concentration 50; D019476:Insect Proteins; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011803:Quinine / Q000494:pharmacology*; D016415:Sequence Alignment; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D000962:Antimalarials; D019476:Insect Proteins; D015800:Protozoan Proteins; D017923:Sodium-Hydrogen Exchangers; D002738:Chloroquine; D011803:Quinine