Genetic diversity of the Pvk12 gene in Plasmodium vivax from the China-Myanmar border area

Malar J. 2016 Nov 4;15(1):528. doi: 10.1186/s12936-016-1592-z.

Abstract

Background: Plasmodium falciparum resistance to artemisinin emerged in the Greater Mekong Sub-region has been associated with mutations in the propeller domain of the kelch gene Pfk13.

Methods: Here the polymorphisms in Pvk12 gene, the orthologue of Pfk13 in Plasmodium vivax, were determined by PCR and sequencing in 262 clinical isolates collected in recent years (2012-2015) from the China-Myanmar border area.

Results: Sequencing of full-length Pvk12 genes from these isolates identified three synonymous mutations (N172N, S360S, S697S) and one non-synonymous mutation M124I, all of which were at very low prevalence (2.0-3.1%). Moreover, these mutations were non-overlapping between the two study sites on both sides of the border. Molecular evolutionary analysis detected signature of purifying selection on Pvk12.

Conclusions: There is no direct evidence that Pvk12 is involved in artemisinin resistance in P. vivax, but it remains a potential candidate requiring further investigation. Continuous monitoring of potential drug resistance in this parasite is needed in order to facilitate the regional malaria elimination campaign.

Keywords: Malaria; Molecular surveillance; Plasmodium vivax; Polymorphism; Pvk12 gene.

MeSH terms

  • Antimalarials / pharmacology
  • Artemisinins / pharmacology
  • China
  • Drug Resistance*
  • Humans
  • Lactones / pharmacology
  • Mutation
  • Myanmar
  • Plasmodium vivax / drug effects
  • Plasmodium vivax / genetics*
  • Plasmodium vivax / isolation & purification*
  • Polymorphism, Genetic*
  • Protozoan Proteins / genetics*
  • Sequence Analysis, DNA

Substances

  • Antimalarials
  • Artemisinins
  • Lactones
  • Protozoan Proteins
  • artemisin