Single-nucleotide polymorphism and copy number variation of the multidrug resistance-1 locus of Plasmodium vivax: Local and global patterns

Rosa Del Carmen Miluska Vargas-Rodríguez, Melissa Da Silva Bastos, Maria José Menezes, Pamela Orjuela-Sánchez, Marcelo U. Ferreira

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish
Pages (from-to)813-821
Number of pages9
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume87
Issue number5
DOIs
StatePublished - Nov 2012
Externally publishedYes

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