title: Single-nucleotide polymorphism and copy number variation of the multidrug resistance-1 locus of Plasmodium vivax: local and global patterns.
abstract: Emerging resistance to chloroquine (CQ) poses a major challenge for Plasmodium vivax malaria control, and nucleotide substitutions and copy number variation in the P. vivax multidrug resistance 1 (pvmdr-1) locus, which encodes a digestive vacuole membrane transporter, may modulate this phenotype. We describe patterns of genetic variation in pvmdr-1 alleles from Acre and Amazonas in northwestern Brazil, and compare then with those reported in other malaria-endemic regions. The pvmdr-1 mutation Y976F, which is associated with CQ resistance in Southeast Asia and Oceania, remains rare in northwestern Brazil (1.8%) and its prevalence mirrors that of CQ resistance worldwide. Gene amplification of pvmdr-1, which is associated with mefloquine resistance but increased susceptibility to CQ, remains relatively rare in northwestern Brazil (0.9%) and globally (< 4%), but became common (> 10%) in Tak Province, Thailand, possibly because of drug-mediated selection. The global database we have assembled provides a baseline for further studies of genetic variation in pvmdr-1 and drug resistance in P. vivax malaria.
authors.affiliation: Department of Parasitology, University of São Paulo, São Paulo, Brazil.
authors.forename: Rosa del Carmen Miluska
authors.initials: Rdel C
authors.lastname: Vargas-Rodríguez
authors.forename: Melissa
authors.initials: M
authors.lastname: da Silva Bastos
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Menezes
authors.forename: Pamela
authors.initials: P
authors.lastname: Orjuela-Sánchez
authors.forename: Marcelo U
authors.initials: MU
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D001483:Base Sequence; D056915:DNA Copy Number Variations; D017931:DNA Primers; D014644:Genetic Variation; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010966:Plasmodium vivax / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C541684:Mdr1 protein, Plasmodium vivax