title: Brazilian Plasmodium falciparum isolates: investigation of candidate polymorphisms for artemisinin resistance before introduction of artemisinin-based combination therapy.
abstract: BACKGROUND
  This study was performed to better understand the genetic diversity of known polymorphisms in pfatpase6 and pfmdr1 genes before the introduction of ACT in Brazil, in order to get a genotypic snapshot of Plasmodium falciparum parasites that may be used as baseline reference for future studies.
  
  
  METHODS
  Parasites from P. falciparum samples collected in 2002, 2004 and 2006-2007 were genotyped using PCR and DNA sequencing at codons 86, 130, 184, 1034, 1042, 1109 and 1246 for pfmdr1 gene, and 243, 263, 402, 431, 623, 630, 639, 683, 716, 776, 769 and 771 for pfatpase6 gene.
  
  
  RESULTS
  A pfmdr1 haplotype NEF/CDVY was found in 97% of the samples. In the case of pfatpase6, four haplotypes, wild-type (37%), 630 S (35%), 402 V (5%) and double-mutant 630 S + 402 V (23%), were detected.
  
  
  CONCLUSIONS
  Although some polymorphism in pfmdr1 and pfatpase6 were verified, no reported haplotypes in both genes that may mediate altered response to ACT was detected before the introduction of this therapy in Brazil. Thus, the haplotypes herein described can be very useful as a baseline reference of P. falciparum populations without ACT drug pressure.
authors.affiliation: Laboratory of Malaria Research, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro (RJ), Brazil.
authors.forename: Bianca E
authors.initials: BE
authors.lastname: Gama
authors.forename: Natália K Almeida
authors.initials: NK
authors.lastname: de Oliveira
authors.forename: José M
authors.initials: JM
authors.lastname: de Souza
authors.forename: Fátima
authors.initials: F
authors.lastname: Santos
authors.forename: Leonardo J M
authors.initials: LJ
authors.lastname: de Carvalho
authors.forename: Yonne F C
authors.initials: YF
authors.lastname: Melo
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Cláudio T
authors.initials: CT
authors.lastname: Daniel-Ribeiro
authors.forename: Maria de Fátima
authors.initials: Mde F
authors.lastname: Ferreira-da-Cruz
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D001938:Brazil; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000251:Adenosine Triphosphatases; D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C031327:artemisinin