scholarly journals Are Transporter Genes Other than the Chloroquine Resistance Locus (pfcrt) and Multidrug Resistance Gene (pfmdr) Associated with Antimalarial Drug Resistance?

2005 ◽  
Vol 49 (9) ◽  
pp. 3990-3990 ◽  
Author(s):  
Timothy J. C. Anderson ◽  
Shalini Nair ◽  
Huang Qin ◽  
Sittaporn Singlam ◽  
Alan Brockman ◽  
...  
2021 ◽  
Vol 5 ◽  
pp. 8-14
Author(s):  
Al-Mukhtar Yahuza Adamu ◽  
Olayeni Stephen Olonitola ◽  
Helen Ileigo Inabo ◽  
Ahmad Babangida Suleiman

Objectives: In 2018, malaria claimed an estimated 380,000 lives in African region, with Nigeria accounting for 24.0% (91,368) of malaria deaths from the region. Mutations in Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr-1) genes had reduced the effective use of artemisinin combination therapy through the development of resistance to these antimalarial agents. Our study set out to determine the antimalarial drug resistance polymorphisms in Pfcrt and Pfmdr-1 genes of P. falciparum isolates among patients in Kano State, Nigeria. Material and Methods: Malaria positive samples were collected across the three senatorial districts of Kano State. The samples were amplified using nested polymerase chain reaction to detect the Pfcrt and Pfmdr-1 genes. The amplicons were sequenced and bioinformatic analysis was done using CLC Sequence viewer 8.0 and BioEdit sequence alignment editor to detect the single-nucleotide polymorphisms. Results: In the Pfcrt gene, CVIET haplotype was seen in 26.2% of the samples while only two samples showed the 86Y mutation in the Pfmdr-1 gene. All the 86Y mutations and majority of the CVIET haplotypes were detected in the patients from rural settings where some of them noted that they consumed modern and traditional (herbs) antimalarial agents. One sample was observed to have the CVIET haplotype and N86Y mutation while the other five CVIET haplotypes were seen in five separate samples. A new mutation V62A was found in the Pfmdr-1 gene as observed in one of the sample. Conclusion: It is imperative to ensure the rational use of the right antimalarial agents and employ continuous resistance surveillance/mapping to ensure synergy in malaria containment and elimination strategies.


Parasitology ◽  
1993 ◽  
Vol 106 (2) ◽  
pp. 107-115 ◽  
Author(s):  
R. M. Ekong ◽  
K. J. H. Robson ◽  
D. A. Baker ◽  
D. C. Warhurst

SUMMARYHomologues of the mammalian multidrug resistance gene have been identified in isolates and clones of Plasmodium falciparum and designated pfmdr1 and pfmdr2. Mutations in pfmdr1 have been associated with chloroquine resistance but confirmation could not be obtained in a genetic cross. We have examined the copy number and expression of pfmdr1 and pfmdr2 in chloroquine-sensitive and -resistant P. falciparum and have found no relationship between the copy number of either gene and chloroquine resistance. However, a marked correlation was seen between levels of mRNA transcribed for each gene and chloroquine resistance. Two transcripts of pfmdr1 were detected, and in the asexual blood cycle an 8 kb transcript appeared first, followed by the appearance of a 7 kb species.


Nature ◽  
1990 ◽  
Vol 345 (6272) ◽  
pp. 255-258 ◽  
Author(s):  
S. J. Foote ◽  
D. E. Kyle ◽  
R. K. Martin ◽  
A. M. J. Oduola ◽  
K. Forsyth ◽  
...  

2014 ◽  
Vol 58 (12) ◽  
pp. 7032-7040 ◽  
Author(s):  
Nathalie Wurtz ◽  
Bécaye Fall ◽  
Aurélie Pascual ◽  
Mansour Fall ◽  
Eric Baret ◽  
...  

ABSTRACTThe involvement ofPfmdr1(Plasmodium falciparummultidrug resistance 1) polymorphisms in antimalarial drug resistance is still debated. Here, we evaluate the association between polymorphisms inPfmdr1(N86Y, Y184F, S1034C, N1042D, and D1246Y) andPfcrt(K76T) andin vitroresponses to chloroquine (CQ), mefloquine (MQ), lumefantrine (LMF), quinine (QN), monodesethylamodiaquine (MDAQ), and dihydroartemisinin (DHA) in 174Plasmodium falciparumisolates from Dakar, Senegal. ThePfmdr186Y mutation was identified in 14.9% of the samples, and the 184F mutation was identified in 71.8% of the isolates. No 1034C, 1042N, or 1246Y mutations were detected. ThePfmdr186Y mutation was significantly associated with increased susceptibility to MDAQ (P= 0.0023), LMF (P= 0.0001), DHA (P= 0.0387), and MQ (P= 0.00002). The N86Y mutation was not associated with CQ (P= 0.214) or QN (P= 0.287) responses. ThePfmdr1184F mutation was not associated with various susceptibility responses to the 6 antimalarial drugs (P= 0.168 for CQ, 0.778 for MDAQ, 0.324 for LMF, 0.961 for DHA, 0.084 for QN, and 0.298 for MQ). ThePfmdr186Y-Y184 haplotype was significantly associated with increased susceptibility to MDAQ (P= 0.0136), LMF (P= 0.0019), and MQ (P= 0.0001). The additionalPfmdr186Y mutation increased significantly thein vitrosusceptibility to MDAQ (P< 0.0001), LMF (P< 0.0001), MQ (P< 0.0001), and QN (P= 0.0026) in wild-typePfcrtK76 parasites. The additionalPfmdr186Y mutation significantly increased thein vitrosusceptibility to CQ (P= 0.0179) inPfcrt76T CQ-resistant parasites.


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