Mutation in pfmdr1 gene in chloroquine-resistant Plasmodium falciparum isolates, Southeast Iran

Background: Malaria is an infectious disease caused by Plasmodium sp., that still prevalence in some part of Indonesia. District of Pesawaran is one of malaria endemic area in the Province of Lampung. The purpose of this study was to evaluate the efficacy of the ACT treatment in the District of Pesawaran Province of Lampung, Indonesia from Dec 2012 to Jul 2013 and the genetic variation of the Plasmodium falciparum also studied. Methods: This study was observational analytic study of falciparum malaria patients treated with ACT and primaquine (DHP-PQ and AAQ-PQ) at Hanura Primary Health Centre (Puskesmas). DNA isolation was done with QIAmp DNA Mini Kit. Amplification of PfMDR1, MSP1, and MSP2 genes was done with appropriate forward and reverse primer and procedures optimized first. PCR Product of PfMDR1 gene was prepared for sequencing. Data analysis was done with MEGA 6 software. Results: The results of this research are DHP-PQ effectiveness was still wellness among falciparum malaria patients in District of Pesawaran, Province of Lampung, Indonesia. There is Single-nucleotide mutation of N86Y of PfMDR1 gene. The dominant alleles found are MAD20 and 3D7 alleles with Multiplicity of Infection (MOI) are low. Conclusion: Therapy of DHP-PQ as an antimalarial falciparum in Pesawaran District, Lampung, Indonesia is still good. The genetic variation found was the SNP on the N86Y PfMDR1 gene, with dominant allele MAD20 and 3D7.

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Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number

The Lancet ◽

10.1016/s0140-6736(04)16767-6 ◽

2004 ◽

Vol 364 (9432) ◽

pp. 438-447 ◽

Cited By ~ 522

Author(s):

Ric N Price ◽

Anne-Catrin Uhlemann ◽

Alan Brockman ◽

Rose McGready ◽

Elizabeth Ashley ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Pfmdr1 Gene

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LACK OF PREDICTION OF MEFLOQUINE AND MEFLOQUINE-ARTESUNATE TREATMENT OUTCOME BY MUTATIONS IN THE PLASMODIUM FALCIPARUM MULTIDRUG RESISTANCE 1 (PFMDR1) GENE FOR PLASMODIUM FALCIPARUM MALARIA IN PERU

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.2003.68.107 ◽

2003 ◽

Vol 68 (1) ◽

pp. 107-110 ◽

Cited By ~ 17

Author(s):

DYLAN R. PILLAI ◽

TRENTON K. RUEBUSH ◽

YSABEL MONTOYA ◽

KEVIN C. KAIN ◽

GISELY HIJAR ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Treatment Outcome ◽

Multidrug Resistance ◽

Falciparum Malaria ◽

Plasmodium Falciparum Malaria ◽

Pfmdr1 Gene

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A P-glycoprotein homologue of Plasmodium falciparum is localized on the digestive vacuole.

The Journal of Cell Biology ◽

10.1083/jcb.113.5.1033 ◽

1991 ◽

Vol 113 (5) ◽

pp. 1033-1042 ◽

Cited By ~ 177

Author(s):

A F Cowman ◽

S Karcz ◽

D Galatis ◽

J G Culvenor

Keyword(s):

Plasmodium Falciparum ◽

Gene Copy Number ◽

Chloroquine Resistance ◽

Gene Copy ◽

Striking Similarity ◽

Multi Drug Resistance ◽

Digestive Vacuole ◽

Pfmdr1 Gene ◽

P Glycoprotein ◽

Quantitative Immunoblotting

Resistance to chloroquine in Plasmodium falciparum bears a striking similarity to the multi-drug resistance (MDR) phenotype of mammalian tumor cells which is mediated by overexpression of P-glycoprotein. We show here that the P. falciparum homologue of the P-glycoprotein (Pgh1) is a 160,000-D protein that is expressed throughout the asexual erythrocytic life cycle of the parasite. Quantitative immunoblotting analysis has shown that the protein is expressed at approximately equal levels in chloroquine resistant and sensitive isolates suggesting that overexpression of Pgh1 is not essential for chloroquine resistance. The chloroquine-resistant cloned line FAC8 however, does express approximately threefold more Pgh1 protein than other isolates which is most likely because of the increased pfmdr1 gene copy number present in this isolate. Immunofluorescence and immunoelectron microscopy has demonstrated that Pgh1 is localized on the membrane of the digestive vacuole of mature parasites. This subcellular localization suggests that Pgh1 may modulate intracellular chloroquine concentrations and has important implications for the normal physiological function of this protein.

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Pfmdr1 gene polymorphism of Plasmodium falciparum isolates from asymptomatic individuals of Dienga, southeastern Gabon

Journal of Parasitic Diseases Diagnosis and Therapy ◽

10.4066/2591-7846.1000024 ◽

2018 ◽

Vol 03 (01) ◽

Author(s):

Irene Pegha-Moukandja ◽

Lady Charlene Kouna ◽

Sydney Maghendji-Nzdondo ◽

Jean Claude Biteghe-Bi-Essone ◽

Dominique Fatima Voumbo-Matoumona ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Gene Polymorphism ◽

Pfmdr1 Gene ◽

Asymptomatic Individuals

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Amplification of the multidrug resistance gene pfmdr1 in Plasmodium falciparum has arisen as multiple independent events

Molecular and Cellular Biology ◽

10.1128/mcb.11.10.5244-5250.1991 ◽

1991 ◽

Vol 11 (10) ◽

pp. 5244-5250

Author(s):

T Triglia ◽

S J Foote ◽

D J Kemp ◽

A F Cowman

Keyword(s):

Polymerase Chain Reaction ◽

Plasmodium Falciparum ◽

Multidrug Resistance ◽

Tumor Cells ◽

Yeast Artificial Chromosome ◽

Chloroquine Resistance ◽

Chain Reaction ◽

Pfmdr1 Gene ◽

Independent Events ◽

Polymerase Chain

The multidrug resistance (MDR) phenotype in mammalian tumor cells can involve amplification of mdr genes that results in overexpression of the protein product termed P-glycoprotein. Chloroquine resistance (CQR) in Plasmodium falciparum has similarities with the MDR phenotype in tumor cells, and some isolates of P. falciparum have amplified levels of the pfmdr1 gene. To investigate the nature and origin of pfmdr1 amplicons, we have cloned large regions of a 110-kb amplicon from the CQR cloned isolate B8 by using the yeast artificial chromosome system. We have identified and sequenced the breakpoints of the amplicon by a novel method employing inverted polymerase chain reaction that is applicable to analysis of any large-scale repeat. We show that the five copies of the amplicon in this isolate are in a head to tail configuration. A string of 30 A's flank the breakpoints on each side of the amplified segment, suggesting a mechanism for the origin of the tandem amplification. Polymerase chain reaction analysis with oligonucleotides that cross the B8 breakpoint has shown in 26 independent CQR isolates, 16 of which contain amplified copies of pfmdr1, that amplification of the pfmdr1 gene in P. falciparum has arisen as multiple independent events. These results suggest that this region of the genome is under strong selective pressure.

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