The F423Y mutation in the pfmdr2 gene and mutations N51I, C59R, and S108N in the pfdhfr gene are independently associated with pyrimethamine resistance in Plasmodium falciparum isolates

Antimicrob Agents Chemother. 2012 May;56(5):2750-2. doi: 10.1128/AAC.05618-11. Epub 2012 Feb 6.

Abstract

Screening for in vitro susceptibility to pyrimethamine and sequencing of the pfmdr2 and pfdhfr genes were performed in 140 Plasmodium falciparum isolates. The risk of in vitro resistance to pyrimethamine was analyzed with a logistic regression model. The mutation F423Y in pfmdr2 (odds ratio [OR] = 2.12 [confidence interval {CI}, 1.02 to 4.59]; P = 0.0489) and the mutation N51I, C59R, or S108N in pfdhfr (OR = 42.34 [CI, 5.52 to 324.61]; P = 0.0003) were independently associated with in vitro resistance to pyrimethamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / pharmacology
  • Drug Resistance / genetics*
  • Folic Acid Antagonists / pharmacology*
  • Genes, Protozoan*
  • Humans
  • Logistic Models
  • Malaria, Falciparum / parasitology
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multivariate Analysis
  • Mutation
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / isolation & purification
  • Polymerase Chain Reaction
  • Pyrimethamine / pharmacology*
  • Sequence Analysis, DNA
  • Tetrahydrofolate Dehydrogenase / genetics*

Substances

  • Antimalarials
  • Folic Acid Antagonists
  • Mdr2 protein, Plasmodium falciparum
  • Multidrug Resistance-Associated Proteins
  • Tetrahydrofolate Dehydrogenase
  • Pyrimethamine