title: Association of microsatellite variations of Plasmodium falciparum Na+/H+ exchanger (Pfnhe-1) gene with reduced in vitro susceptibility to quinine: lack of confirmation in clinical isolates from Africa.
abstract: We sought to test the association of polymorphisms in Plasmodium falciparum nhe-1 (Pfnhe-1, gene PF13_0019) with in vitro susceptibility to quinine, which was previously reported in a limited number of reference strains or culture-adapted isolates. Determination of in vitro susceptibility to quinine, genotyping of Pfnhe-1 ms4760 microsatellite and polymorphism in codon 76 of Pfcrt were performed for 83 isolates obtained from symptomatic malaria-infected travelers returning from various African countries to France or from subjects living in Madagascar. Nineteen different ms4760 microsatellite profiles of Pfnhe-1 were found including 14 not previously described. Multivariate analysis showed no significant association between the in vitro susceptibility to quinine with particular ms4760 profiles. Contrary to previous reports, we only observed that the number of NHNDNHNNDDD repeats was positively associated with the increased IC50 of QN (P = 0.01). We concluded that the studied polymorphisms in Pfnhe-1 did not appear as valid molecular markers of in vitro susceptibility to quinine in P. falciparum isolates from Africa. Because we did not include any isolate of Asian origin in our series, these results did not exclude the possibility of regional associations, for example in South-East Asia.
authors.affiliation: Institut Pasteur de Madagascar, Unité de Recherche sur le Paludisme, Antananarivo, Madagascar, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Andriantsoanirina
authors.forename: Didier
authors.initials: D
authors.lastname: Ménard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Rabearimanana
authors.forename: Véronique
authors.initials: V
authors.lastname: Hubert
authors.forename: Christiane
authors.initials: C
authors.lastname: Bouchier
authors.forename: Magali
authors.initials: M
authors.lastname: Tichit
authors.forename: Jacques Le
authors.initials: JL
authors.lastname: Bras
authors.forename: Rémy
authors.initials: R
authors.lastname: Durand
mesh_terms: D000349:Africa / Q000453:epidemiology; D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics; D011803:Quinine / Q000494:pharmacology*; D016415:Sequence Alignment; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D015800:Protozoan Proteins; D017923:Sodium-Hydrogen Exchangers; D002738:Chloroquine; D011803:Quinine