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Sequence and gene expression of chloroquine resistance transporter (<it>pfcrt</it>) in the association of <it>in vitro </it>drugs resistance of <it>Plasmodium falciparum</it>

Bray Patrick G, Owen Andrew, Johnson David and 4 more

Malaria Journal · 2011

doi:10.1186/1475-2875-10-42 (opens in a new tab)

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Abstract

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>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 <it>pfcrt </it>and resistance to chloroquine in <it>P. falciparum</it>. Although these mutations are predictive of chloroquine resistance, they are not quantitatively predictive of the degree of resistance.</p> <p>Methods</p> <p>In this study, a total of 95 recently adapted <it>P. falciparum </it>isolates from Thailand were included in the analysis. Parasites were characterized for their drug susceptibility phenotypes and genotypes with respect to <it>pfcrt</it>. From the original 95 isolates, 20 were selected for complete <it>pfcrt </it>sequence analysis.</p> <p>Results</p> <p>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, <it>pfcrt </it>and <it>pfmdr1 </it>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.</p> <p>Conclusion</p> <p>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 <it>pfcrt</it>.</p>

Abstract licence: CC BY-NC-ND

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