title: Global analysis of Plasmodium falciparum Na(+)/H(+) exchanger (pfnhe-1) allele polymorphism and its usefulness as a marker of in vitro resistance to quinine.
abstract: The aim of this study was to provide a comprehensive analysis of the worldwide genetic polymorphism of ms4760 alleles of the pfnhe-1 gene and to discuss their usefulness as molecular marker of quinine resistance (QNR). A new numbering of ms4760 allele, classification grouping ms4760 alleles according to the number of DNNND and DDNHNDNHNND repeat motifs in blocks II and V was also proposed. A total of 1508 ms4760 sequences from isolates, culture-adapted parasites or reference strains from various geographical regions were retrieved from GenBank (last update on 15th June 2012) or from publications and were used for genetic analyses. The association of different alleles of pfnhe-1 with resistance to quinoline antimalarial drugs showed marked geographic disparities. The validity and reliability of candidate polymorphisms in pfnhe-1 gene as molecular markers of QNR appeared restricted to endemic areas from South Asia or possibly East African countries and needs to be confirmed.
authors.affiliation: Unité d'Epidémiologie Moléculaire du Paludisme, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
authors.forename: Didier
authors.initials: D
authors.lastname: Ménard
authors.affiliation: Laboratoire de Parasitologie-Mycologie, Hôpital Avicenne, AP-HP, Bobigny, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Andriantsoanirina
authors.affiliation: Unité d'Epidémiologie Moléculaire du Paludisme, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
authors.forename: Nimol
authors.initials: N
authors.lastname: Khim
authors.affiliation: Ministère de la Santé, du Planning Familial et de la Protection Sociale, Programme National de Lutte contre le Paludisme, BP 1869 Antananarivo, Madagascar.
authors.forename: Arsène
authors.initials: A
authors.lastname: Ratsimbasoa
authors.affiliation: Unité d'Epidémiologie Moléculaire du Paludisme, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
authors.forename: Benoit
authors.initials: B
authors.lastname: Witkowski
authors.affiliation: Unité d'Epidémiologie Moléculaire du Paludisme, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
authors.forename: Christophe
authors.initials: C
authors.lastname: Benedet
authors.affiliation: Unité d'Epidémiologie Moléculaire du Paludisme, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
authors.forename: Lydie
authors.initials: L
authors.lastname: Canier
authors.affiliation: Unité d'Immunologie Moléculaire des Parasites, Institut Pasteur & Centre National de la Recherche Scientifique, Unité de Recherche Associée 2581, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.affiliation: Laboratoire de Parasitologie-Mycologie, Hôpital Avicenne, AP-HP, Bobigny, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Durand
keywords: Genetic polymorphism; Malaria; Na+/H+ exchanger; Plasmodium falciparum; Quinine resistance