Document Detail


Linkage disequilibrium between two chromosomally distinct loci associated with increased resistance to chloroquine in Plasmodium falciparum.
MedLine Citation:
PMID:  11085219     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chloroquine-resistance in Plasmodium falciparum is associated with polymorphisms in a locus on or near the cg2 gene on chromosome 7, and in the pfmdr1 gene on chromosome 5. In this study we typed P. falciparum DNA from uncomplicated malaria cases in The Gambia in 1990, 1995 and 1996 for size polymorphism in the omega repeat of cg2, for sequence polymorphisms in pfmdr1 at codons 86 and 184, in dhfr at codon 108 and in the msp2 gene. Chloroquine sensitivity tests were conducted in vitro. A significant but incomplete association was found between the presence of the cg2 Dd2-like omega repeat size polymorphism and in vitro resistance, and between the tyr-86 allele of pfmdr1 and in vitro resistance. Furthermore there was strong linkage disequilibrium between the pfmdr1 asn-86 allele and the cg2 not Dd2-like omega repeat allele located on different chromosomes. In contrast, no linkage disequilibrium was found between these alleles and either the dhfr ser-108 allele or the msp2 IC sequence polymorphism. No significant linkage was measured between pfmdr1 asn-86 and phe-184 although these loci are separated only by 296 base pairs. Our results suggest that genetic elements linked to the cg2 and the pfmdr1 genes are important determinants of chloroquine resistance. It can be concluded that the observed linkage disequilibrium is maintained epistatically through selection by chloroquine.
Authors:
M T Duraisingh; L V von Seidlein; A Jepson; P Jones; I Sambou; M Pinder; D C Warhurst
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Parasitology     Volume:  121 ( Pt 1)     ISSN:  0031-1820     ISO Abbreviation:  Parasitology     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-11-21     Completed Date:  2001-01-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0401121     Medline TA:  Parasitology     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
Affiliation:
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK.
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters*
Animals
Antimalarials / pharmacology*
Chloroquine / pharmacology*
Drug Resistance / genetics
Genes, Protozoan
Humans
Linkage Disequilibrium* / genetics
Malaria, Falciparum / parasitology*
Parasitic Sensitivity Tests / methods
Plasmodium falciparum / drug effects*,  genetics*
Polymorphism, Genetic / genetics
Protozoan Proteins / genetics
Chemical
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Antimalarials; 0/CG2 protein, Plasmodium falciparum; 0/Protozoan Proteins; 0/mdr gene protein, Plasmodium; 54-05-7/Chloroquine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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