Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries

Feng Lu, Chae Seung Lim, Deok Hwas Nam, Kwonkee Kim, Khin Lin, Tong Soo Kim, Hyeong Woo Lee, Jun Hu Chen, Yue Wang, Jetsumon Sattabongkot, Eun Taek Han

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Abstract

Treatment failure of chloroquine for Plasmodium vivax infection has increased in endemic countries. However, the molecular mechanisms for resistance and in vitro susceptibility of P. vivax to chloroquine remain elusive. We investigated the prevalence of mutations in the pvmdr1 and pvcrt-o genes, and the copy number of the pvmdr1 gene in isolates from the Republic of Korea (ROK), Thailand, the Union of Myanmar (Myanmar), and Papua New Guinea (PNG). We also measured in vitro susceptibility of Korean isolates to antimalarial drugs. The pvmdr1 analysis showed that mutations at amino acid position Y976F of pvmdr1 were found in isolates from Thailand (17.9%), Myanmar (13.3%), and PNG (100%), but none from the ROK, and mutation at position F1076L was present in isolates from the ROK (100%), Thailand (60.7%), and Myanmar (46.7%). One copy of the pvmdr1 gene was observed in most isolates and double copy numbers of the gene were observed in two Thai isolates. In the exons of the pvcrt-o gene that were sequenced, a K10 insertion was present in isolates from Thailand (56.0%) and Myanmar (46.2%), and the wild type was found in all Korean isolates. The results suggest that gene polymorphisms and copy number variation was observed in isolates of P. vivax from Southeast Asian countries. In Korean isolates polymorphism as limited to the F1076L variant, and no isolates with high level of resistance were found by in vitro susceptibility determinations. Moreover, our results provide a baseline for future prospective drug studies in malaria-endemic areas.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalActa Tropica
Volume117
Issue number2
DOIs
Publication statusPublished - 2011 Feb 1

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Myanmar
Vivax Malaria
Plasmodium vivax
Genetic Polymorphisms
malaria
Thailand
Republic of Korea
genetic polymorphism
Gene Dosage
South Korea
drugs
gene dosage
Papua New Guinea
chloroquine
Pharmaceutical Preparations
Genes
Chloroquine
mutation
genes
Mutation

Keywords

  • Copy number
  • Drug resistance gene
  • In vitro drug susceptibility
  • Plasmodium vivax
  • Pvcrt-o
  • Pvmdr1
  • Single nucleotide polymorphisms (SNPs)

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries. / Lu, Feng; Lim, Chae Seung; Nam, Deok Hwas; Kim, Kwonkee; Lin, Khin; Kim, Tong Soo; Lee, Hyeong Woo; Chen, Jun Hu; Wang, Yue; Sattabongkot, Jetsumon; Han, Eun Taek.

In: Acta Tropica, Vol. 117, No. 2, 01.02.2011, p. 69-75.

Research output: Contribution to journalArticle

Lu, Feng ; Lim, Chae Seung ; Nam, Deok Hwas ; Kim, Kwonkee ; Lin, Khin ; Kim, Tong Soo ; Lee, Hyeong Woo ; Chen, Jun Hu ; Wang, Yue ; Sattabongkot, Jetsumon ; Han, Eun Taek. / Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries. In: Acta Tropica. 2011 ; Vol. 117, No. 2. pp. 69-75.
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abstract = "Treatment failure of chloroquine for Plasmodium vivax infection has increased in endemic countries. However, the molecular mechanisms for resistance and in vitro susceptibility of P. vivax to chloroquine remain elusive. We investigated the prevalence of mutations in the pvmdr1 and pvcrt-o genes, and the copy number of the pvmdr1 gene in isolates from the Republic of Korea (ROK), Thailand, the Union of Myanmar (Myanmar), and Papua New Guinea (PNG). We also measured in vitro susceptibility of Korean isolates to antimalarial drugs. The pvmdr1 analysis showed that mutations at amino acid position Y976F of pvmdr1 were found in isolates from Thailand (17.9{\%}), Myanmar (13.3{\%}), and PNG (100{\%}), but none from the ROK, and mutation at position F1076L was present in isolates from the ROK (100{\%}), Thailand (60.7{\%}), and Myanmar (46.7{\%}). One copy of the pvmdr1 gene was observed in most isolates and double copy numbers of the gene were observed in two Thai isolates. In the exons of the pvcrt-o gene that were sequenced, a K10 insertion was present in isolates from Thailand (56.0{\%}) and Myanmar (46.2{\%}), and the wild type was found in all Korean isolates. The results suggest that gene polymorphisms and copy number variation was observed in isolates of P. vivax from Southeast Asian countries. In Korean isolates polymorphism as limited to the F1076L variant, and no isolates with high level of resistance were found by in vitro susceptibility determinations. Moreover, our results provide a baseline for future prospective drug studies in malaria-endemic areas.",
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AU - Lim, Chae Seung

AU - Nam, Deok Hwas

AU - Kim, Kwonkee

AU - Lin, Khin

AU - Kim, Tong Soo

AU - Lee, Hyeong Woo

AU - Chen, Jun Hu

AU - Wang, Yue

AU - Sattabongkot, Jetsumon

AU - Han, Eun Taek

PY - 2011/2/1

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