Dataset Information

Human Genetic Markers and Structural Prediction of Plasmodium falciparum Multidrug Resistance Gene (pfmdr1) for Ligand Binding in Pregnant Women Attending General Hospital Minna.

ABSTRACT: The study aims to determine the association of malaria infection with ABO blood groups and genotype and also to detect point mutations at positions 86, 184, 1034, and 1042 of the Plasmodium falciparum multidrug resistance gene (pfmdr1) in blood samples collected from pregnant women attending General Hospital Minna. Out of 250 pregnant women screened, 39 (15.60%) had malaria infection. Prevalence was higher in women, during the third trimester (46.15%), genotype AA (64.10%), and O blood group (53.84%) individuals when compared with others. There was significant (p < 0.05) decrease in Packed Cell Volume (PCV), hemoglobin (HGB), Red Blood Cells (RBC), and platelet (PLC) count in infected group when compared with noninfected group. Although, two of the isolates showed disrupted protein sequence at codon 1034-1042, no mutation was found in any of the P. falciparum isolates. Structural prediction of chemical ligand led to the identification of Neu5Ac?2-3Gal?1-3/?1-4Glc/GlcNAc. This compound can theoretically bind and change the functional integrity of the pfmdr1 protein, thus providing a new window for malaria drug target.

SUBMITTER: Lawal B

PROVIDER: S-EPMC5976944 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Human Genetic Markers and Structural Prediction of Plasmodium falciparum Multidrug Resistance Gene (pfmdr1) for Ligand Binding in Pregnant Women Attending General Hospital Minna.

Lawal B B Shittu O K OK Abubakar A A Kabiru A Y AY

Journal of environmental and public health 20180516

The study aims to determine the association of malaria infection with ABO blood groups and genotype and also to detect point mutations at positions 86, 184, 1034, and 1042 of the Plasmodium falciparum multidrug resistance gene (pfmdr1) in blood samples collected from pregnant women attending General Hospital Minna. Out of 250 pregnant women screened, 39 (15.60%) had malaria infection. Prevalence was higher in women, during the third trimester (46.15%), genotype AA (64.10%), and O b ...[more]

PMID: 29861750

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Project description:BackgroundAnti-malarial drugs are the major focus in the prevention and treatment of malaria. Artemisinin-based combination therapy (ACT) is the WHO recommended first-line treatment for Plasmodium falciparum malaria across the endemic world. Also ACT is increasingly relied upon in treating Plasmodium vivax malaria where chloroquine is failing. The emergence of artemisinin drug-resistant parasites is a serious threat faced by global malaria control programmes. Therefore, the success of treatment and intervention strategies is highly pegged on understanding the genetic basis of resistance.MethodsHere, resistance in P. falciparum was generated in vitro for artemisinin to produce levels above clinically relevant concentrations in vivo, and the molecular haplotypes investigated. Genomic DNA was extracted using the QIAamp mini DNA kit. DNA sequences of Pfk13, Pfcrt and Pfmdr1 genes were amplified by PCR and the amplicons were successfully sequenced. Single nucleotide polymorphisms were traced by standard bidirectional sequencing and reading the transcripts against wild-type sequences in Codon code Aligner Version 5.1 and NCBI blast.ResultsExposure of parasite strains D6 and W2 to artemisinin resulted in a decrease in parasite susceptibility to artemisinin (W2 and D6) and lumefantrine (D6 only). The parasites exhibited elevated IC50s to multiple artemisinins, with >twofold resistance to artemisinin; however, the resistance index obtained with standard methods was noticeably less than expected for parasite lines recovered from 50 µg/ml 48 h drug pressure. The change in parasite susceptibility was associated with Pfmdr-185K mutation, a mutation never reported before. The Pfcrt-CVMNK genotype (Pfcrt codons 72-76) was retained and notably, the study did not detect any polymorphisms reported to reduce P. falciparum susceptibility in vivo in the coding sequences of the Pfk13 gene.DiscussionThis data demonstrate that P. falciparum has the capacity to develop resistance to artemisinin derivatives in vitro and that this phenotype is achieved by mutations in Pfmdr1, the genetic changes that are also underpinning lumefantrine resistance. This finding is of practical importance, because artemisinin drugs in Kenya are used in combination with lumefantrine for the treatment of malaria.ConclusionArtemisinin resistance phenotype as has been shown in this work, is a decrease in parasites susceptibility to artemisinin derivatives together with the parasite's ability to recover from drug-induced dormancy after exposure to drug dosage above the in vivo clinical concentrations. The study surmises that Pfmdr1 may play a role in the anti-malarial activity of artemisinin.

Dataset Information

Human Genetic Markers and Structural Prediction of Plasmodium falciparum Multidrug Resistance Gene (pfmdr1) for Ligand Binding in Pregnant Women Attending General Hospital Minna.

Publications

Human Genetic Markers and Structural Prediction of <i>Plasmodium falciparum</i> Multidrug Resistance Gene <i>(pfmdr1)</i> for Ligand Binding in Pregnant Women Attending General Hospital Minna.

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Dataset Information

Human Genetic Markers and Structural Prediction of Plasmodium falciparum Multidrug Resistance Gene (pfmdr1) for Ligand Binding in Pregnant Women Attending General Hospital Minna.

Publications

Human Genetic Markers and Structural Prediction of &lt;i&gt;Plasmodium falciparum&lt;/i&gt; Multidrug Resistance Gene &lt;i&gt;(pfmdr1)&lt;/i&gt; for Ligand Binding in Pregnant Women Attending General Hospital Minna.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Human Genetic Markers and Structural Prediction of <i>Plasmodium falciparum</i> Multidrug Resistance Gene <i>(pfmdr1)</i> for Ligand Binding in Pregnant Women Attending General Hospital Minna.