title: Sequence and gene expression of chloroquine resistance transporter (pfcrt) in the association of in vitro drugs resistance of Plasmodium falciparum.
abstract: BACKGROUND
  Plasmodium falciparum chloroquine resistance (CQR) transporter protein (PfCRT) is known to be the important key of CQR. Recent studies have definitively demonstrated a link between mutations in the gene pfcrt and resistance to chloroquine in P. falciparum. Although these mutations are predictive of chloroquine resistance, they are not quantitatively predictive of the degree of resistance.
  
  
  METHODS
  In this study, a total of 95 recently adapted P. falciparum isolates from Thailand were included in the analysis. Parasites were characterized for their drug susceptibility phenotypes and genotypes with respect to pfcrt. From the original 95 isolates, 20 were selected for complete pfcrt sequence analysis.
  
  
  RESULTS
  Almost all of the parasites characterized carried the previously reported mutations K76T, A220S, Q271E, N326S, I356T and R371I. On complete sequencing, isolates were identified with novel mutations at K76A and E198K. There was a suggestion that parasites carrying E198K were less resistant than those that did not. In addition, pfcrt and pfmdr1 gene expression were investigated by real-time PCR. No relationship between the expression level of either of these genes and response to drug was observed.
  
  
  CONCLUSIONS
  Data from the present study suggest that other genes must contribute to the degree of resistance once the resistance phenotype is established through mutations in pfcrt.
authors.affiliation: Faculty of Allied Health Sciences, Thammasat University, Rangsit, Patumthani 12120, Thailand.
authors.forename: Wanna
authors.initials: W
authors.lastname: Chaijaroenkul
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ward
authors.forename: Mathirut
authors.initials: M
authors.lastname: Mungthin
authors.forename: David
authors.initials: D
authors.lastname: Johnson
authors.forename: Andrew
authors.initials: A
authors.lastname: Owen
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Bray
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000962:Antimalarials / Q000494:pharmacology; D001483:Base Sequence; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D015870:Gene Expression; D017125:Genes, Protozoan; D005838:Genotype; D016778:Malaria, Falciparum / Q000469:parasitology; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D013785:Thailand
chemical_list: D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine