Linked Life Data

9364963

Source:http://linkedlifedata.com/resource/pubmed/id/9364963

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-12-23
pubmed:abstractText
Resistance of Plasmodium falciparum to antifolate chemotherapy is a significant problem where combinations such as Fansidar (pyrimethamine-sulfadoxine; PYR-SDX) are used in the treatment of chloroquine-resistant malaria. Antifolate resistance has been associated with variant sequences of dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS), the targets of PYR and SDX respectively. However, while the nature and distribution of mutations in the dhfr gene are well established, this is not yet the case for dhps. We have thus examined by DNA sequence analysis 141 field samples from several geographical regions with differing Fansidar usage (West and East Africa, the Middle East and Viet Nam) to establish a database of the frequency and repertoire of dhps mutations, which were found in 60% of the samples. We have also simultaneously determined from all samples their dhfr sequences, to better understand the relationship of both types of mutation to Fansidar resistance. Whilst the distribution of mutations was quite different across the regions surveyed, it broadly mirrored our understanding of relative Fansidar usage. In samples taken from individual patients before and after drug treatment, we found an association between the more highly mutated forms of dhps and/or dhfr and parasites that were not cleared by antifolate therapy. We also report a novel mutation in a Pakistani sample at position 16 of DHFR (A16S) that is combined with the familiar C59R mutation, but is wild-type at position 108. This is the first observation in a field sample of a mutant dhfr allele where the 108 codon is unchanged.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0166-6851
pubmed:author
pubmed:issnType
Print
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
161-77
pubmed:dateRevised
2010-8-25
pubmed:meshHeading
pubmed-meshheading:9364963-Africa, pubmed-meshheading:9364963-Alleles, pubmed-meshheading:9364963-Animals, pubmed-meshheading:9364963-Antimalarials, pubmed-meshheading:9364963-DNA Mutational Analysis, pubmed-meshheading:9364963-Dihydropteroate Synthase, pubmed-meshheading:9364963-Drug Combinations, pubmed-meshheading:9364963-Drug Resistance, pubmed-meshheading:9364963-Folic Acid Antagonists, pubmed-meshheading:9364963-Genes, Protozoan, pubmed-meshheading:9364963-Humans, pubmed-meshheading:9364963-Malaria, Falciparum, pubmed-meshheading:9364963-Middle East, pubmed-meshheading:9364963-Plasmodium falciparum, pubmed-meshheading:9364963-Point Mutation, pubmed-meshheading:9364963-Pyrimethamine, pubmed-meshheading:9364963-Sulfadoxine, pubmed-meshheading:9364963-Tetrahydrofolate Dehydrogenase, pubmed-meshheading:9364963-Vietnam
pubmed:year
1997
pubmed:articleTitle
Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthetase and dihydrofolate reductase alleles in a large number of field samples of diverse origins.
pubmed:affiliation
Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't