Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah

The successful use of chloroquine(CQ) through the decades finally resulted in CQ resistant(CQR) Plasmodium falciparum. These drug resistant parasites led to high fatality in humans. CQR P. falciparum strains were spread through the world from Colombia and Cambodia-Thailand border within these decade...

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Main Authors: Khin Saw Naing, Shamsul Bahari Shamsudin
Format: Research Report
Language:English
Published: Universiti Malaysia Sabah 2014
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Online Access:https://eprints.ums.edu.my/id/eprint/24833/1/Mutations%20of%20transporter%20genes%20associated%20with%20drug%20resistance%20in%20Plasmodium%20Falciparum%20isolates%20from%20rural%20area%20of%20Sabah.pdf
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spelling my.ums.eprints.248332020-02-03T02:44:29Z https://eprints.ums.edu.my/id/eprint/24833/ Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah Khin Saw Naing Shamsul Bahari Shamsudin SF Animal culture The successful use of chloroquine(CQ) through the decades finally resulted in CQ resistant(CQR) Plasmodium falciparum. These drug resistant parasites led to high fatality in humans. CQR P. falciparum strains were spread through the world from Colombia and Cambodia-Thailand border within these decades. The ATP-binding cassette (ABC) protein plays the major role in drug resistance in P. falciparum. Antimalarial drug resistance was associated with single nucleotide polymorphisms (SNPs) in genes encoding ABC proteins. Three genes which are well studied include pfcrt (Plasmodium falciparum CQ-resistance transporter) pfmdr 1 (Plasmodium falciparum multidrug resistance 1) and pfmrp 1 (Plasmodium falcipi!rum multidrug resistance protein 1) genes. All pfcrt alleles in CQR parasites consistently include mutations for K76T and A220S accompanied by changes in two to six other mutations. Pfcrt K76T SNP is the major molecular determinant of CQR P. falciparum strains. N86Y marker of pfmdr 1 gene and K76T marker of pfcrtgene were prevalent in CQR isolates. Another SNP which is well studied and highly prevalent in pfmdr 1 gene is Y184F. Five SNPs, two SNPs and 1 SNP in pfcrt, pfmdr 1 and pfmrp 1 genes respectively were studied by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and PCR-DNA sequencing methods in the current study. SVMNT and CVIET haplotypes of pfcrt gene were circulating in rural areas of Sabah. The results indicate that the drug resistant markers in drug resistant P. falciparum isolates from rural Sabah were supposed to be pfcrt 76T, 220S and pfmdr 1 84Y. Finally, we have succeeded to identify the molecular markers for CQR Plasmodlum falclparum for the rural areas of Sabah. Universiti Malaysia Sabah 2014 Research Report NonPeerReviewed text en https://eprints.ums.edu.my/id/eprint/24833/1/Mutations%20of%20transporter%20genes%20associated%20with%20drug%20resistance%20in%20Plasmodium%20Falciparum%20isolates%20from%20rural%20area%20of%20Sabah.pdf Khin Saw Naing and Shamsul Bahari Shamsudin (2014) Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah. (Unpublished)
institution Universiti Malaysia Sabah
building UMS Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Sabah
content_source UMS Institutional Repository
url_provider http://eprints.ums.edu.my/
language English
topic SF Animal culture
spellingShingle SF Animal culture
Khin Saw Naing
Shamsul Bahari Shamsudin
Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah
description The successful use of chloroquine(CQ) through the decades finally resulted in CQ resistant(CQR) Plasmodium falciparum. These drug resistant parasites led to high fatality in humans. CQR P. falciparum strains were spread through the world from Colombia and Cambodia-Thailand border within these decades. The ATP-binding cassette (ABC) protein plays the major role in drug resistance in P. falciparum. Antimalarial drug resistance was associated with single nucleotide polymorphisms (SNPs) in genes encoding ABC proteins. Three genes which are well studied include pfcrt (Plasmodium falciparum CQ-resistance transporter) pfmdr 1 (Plasmodium falciparum multidrug resistance 1) and pfmrp 1 (Plasmodium falcipi!rum multidrug resistance protein 1) genes. All pfcrt alleles in CQR parasites consistently include mutations for K76T and A220S accompanied by changes in two to six other mutations. Pfcrt K76T SNP is the major molecular determinant of CQR P. falciparum strains. N86Y marker of pfmdr 1 gene and K76T marker of pfcrtgene were prevalent in CQR isolates. Another SNP which is well studied and highly prevalent in pfmdr 1 gene is Y184F. Five SNPs, two SNPs and 1 SNP in pfcrt, pfmdr 1 and pfmrp 1 genes respectively were studied by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and PCR-DNA sequencing methods in the current study. SVMNT and CVIET haplotypes of pfcrt gene were circulating in rural areas of Sabah. The results indicate that the drug resistant markers in drug resistant P. falciparum isolates from rural Sabah were supposed to be pfcrt 76T, 220S and pfmdr 1 84Y. Finally, we have succeeded to identify the molecular markers for CQR Plasmodlum falclparum for the rural areas of Sabah.
format Research Report
author Khin Saw Naing
Shamsul Bahari Shamsudin
author_facet Khin Saw Naing
Shamsul Bahari Shamsudin
author_sort Khin Saw Naing
title Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah
title_short Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah
title_full Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah
title_fullStr Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah
title_full_unstemmed Mutations of transporter genes associated with drug resistance in Plasmodium Falciparum isolates from rural area of Sabah
title_sort mutations of transporter genes associated with drug resistance in plasmodium falciparum isolates from rural area of sabah
publisher Universiti Malaysia Sabah
publishDate 2014
url https://eprints.ums.edu.my/id/eprint/24833/1/Mutations%20of%20transporter%20genes%20associated%20with%20drug%20resistance%20in%20Plasmodium%20Falciparum%20isolates%20from%20rural%20area%20of%20Sabah.pdf
https://eprints.ums.edu.my/id/eprint/24833/
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