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

Am J Trop Med Hyg. 2012 Nov;87(5):813-21. doi: 10.4269/ajtmh.2012.12-0094. Epub 2012 Sep 4.

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.

MeSH terms

  • Animals
  • Base Sequence
  • DNA Copy Number Variations*
  • DNA Primers
  • Genetic Variation
  • Multidrug Resistance-Associated Proteins / genetics*
  • Plasmodium vivax / drug effects*
  • Plasmodium vivax / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Protozoan Proteins / genetics*

Substances

  • DNA Primers
  • Mdr1 protein, Plasmodium vivax
  • Multidrug Resistance-Associated Proteins
  • Protozoan Proteins