The Lys-76-Thr mutation in PfCRT and chloroquine resistance in Plasmodium falciparum isolates from Uganda

Trans R Soc Trop Med Hyg. Jan-Feb 2002;96(1):91-5. doi: 10.1016/s0035-9203(02)90252-x.

Abstract

Recent molecular studies of chloroquine (CQ) resistance of Plasmodium falciparum have demonstrated an association between a mutation in the PfCRT gene and CQ resistance. We identified wild type and mutant alleles of the PfCRT codon 76 in baseline pre-CQ treatment P. falciparum isolates collected during 1999 and investigated their relationship to CQ efficacy in 3 different sites with different levels of CQ parasite resistance in Uganda. Of 32 isolates from Mulago Hospital, all were mutant (100%), while of 45 isolates from Tororo, 5 (11%) were mixed wild type and mutant and 40 (89%) were mutants only. Of 41 isolates from Apac, 13 (32%) were mixed wild type and mutant whereas 28 (68%) were mutants only. The finding of 100% prevalence of the Thr-76 mutant allele in all isolates at the 3 sites was remarkable. We found no association between the presence of Thr-76 mutation and treatment outcome at all the sites. However, the prevalence of the wild-type Lys-76 allele was higher in Apac, an area with lower CQ parasite resistance, compared to Tororo and Mulago which have relatively higher CQ parasite resistance. The Thr-76 allele as a marker of CQ resistance is probably useful in regions where the allele frequency has not yet plateaued.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / therapeutic use*
  • Chloroquine / therapeutic use*
  • DNA, Protozoan / genetics
  • Drug Resistance / genetics
  • Genotype
  • Humans
  • Malaria, Falciparum / genetics*
  • Membrane Proteins / genetics*
  • Membrane Transport Proteins
  • Mutation / genetics*
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics*
  • Polymerase Chain Reaction / methods
  • Protozoan Proteins
  • Uganda

Substances

  • Antimalarials
  • DNA, Protozoan
  • Membrane Proteins
  • Membrane Transport Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • Chloroquine