Global analysis of Plasmodium falciparum Na+/H+ exchanger (pfnhe-1) allele polymorphism and its usefulness as a marker of in vitro resistance to quinine

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.

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► We compile 1508 ms4760 alleles of the pfnhe-1 gene from various geographical regions.
► New numbering of ms4760 allele and classification grouping alleles are proposed.
► Pfnhe-1 allele polymorphism as a marker of quinine resistance appears restricted to South Asia.