New haplotypes of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene among chloroquine-resistant parasite isolates. 2003

Hadya S Nagesha, and Gerard J Casey, and Karl H Rieckmann, and David J Fryauff, and Budi S Laksana, and John C Reeder, and Jason D Maguire, and J Kevin Baird
The Walter and Eliza Hall Institute for Medical Research, Melbourne, Australia. hadya@wehi.edu.au

Mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene were examined to assess their associations with chloroquine resistance in clinical samples from Armopa (Papua) and Papua New Guinea. In Papua, two of the five pfcrt haplotypes found were new: SVIET from Armopa and CVIKT from an isolate in Timika. There was also a strong association (P < 0.0001) between the pfcrt 76T allele and chloroquine resistance in 50 samples. In Papua New Guinea, mutations in the pfcrt gene were observed in 15 isolates with chloroquine minimum inhibitory concentrations (MICs) of 16-64 pmol, while the remaining six isolates, which had a wild-type pfcrt gene at codon 76, had MICs of 2-8 pmol. These observations confirm that mutations at codon 76 in the pfcrt gene are present in both in vivo and in vitro cases of chloroquine resistance, and that detection of the pfcrt 76T allele could predict potential chloroquine treatment failures.

UI MeSH Term Description Entries
D007214 Indonesia A republic stretching from the Indian Ocean east to New Guinea, comprising six main islands: Java, Sumatra, Bali, Kalimantan (the Indonesian portion of the island of Borneo), Sulawesi (formerly known as the Celebes) and Irian Jaya (the western part of New Guinea). Its capital is Djakarta. The ethnic groups living there are largely Chinese, Arab, Eurasian, Indian, and Pakistani; 85% of the peoples are of the Islamic faith. Celebes,Indonesian New Guinea,Irian Jaya,Java,Madoera,Netherlands East Indies,New Guinea, Indonesian,New Guinea, West,Sulawesi,Sumatra,Timor,West Irian,Bali,East Indies,Madura,Malay Archipelago
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010219 Papua New Guinea A country consisting of the eastern half of the island of New Guinea and adjacent islands, including New Britain, New Ireland, the Admiralty Islands, and New Hanover in the Bismarck Archipelago; Bougainville and Buka in the northern Solomon Islands; the D'Entrecasteaux and Trobriand Islands; Woodlark (Murua) Island; and the Louisiade Archipelago. It became independent on September 16, 1975. Formerly, the southern part was the Australian Territory of Papua, and the northern part was the UN Trust Territory of New Guinea, administered by Australia. They were administratively merged in 1949 and named Papua and New Guinea, and renamed Papua New Guinea in 1971. New Guinea, East,New Guinea, Papua
D010963 Plasmodium falciparum A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics. Plasmodium falciparums,falciparums, Plasmodium
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D002738 Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Aralen,Arechine,Arequin,Chingamin,Chlorochin,Chloroquine Sulfate,Chloroquine Sulphate,Khingamin,Nivaquine,Sulfate, Chloroquine,Sulphate, Chloroquine
D004252 DNA Mutational Analysis Biochemical identification of mutational changes in a nucleotide sequence. Mutational Analysis, DNA,Analysis, DNA Mutational,Analyses, DNA Mutational,DNA Mutational Analyses,Mutational Analyses, DNA
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D006239 Haplotypes The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. Haplotype

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