In vitro sensitivity of Plasmodium falciparum clinical isolates from the China-Myanmar border area to quinine and association with polymorphism in the Na+/H+ exchanger

Hao Meng, Rongping Zhang, Henglin Yang, Qi Fan, Xinzhuan Su, Jun Miao, Liwang Cui, Zhaoqing Yang

Research output: Contribution to journalArticle

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Abstract

Quinine resistance (QNR) in Plasmodium falciparum has been detected in many regions of the world where malaria is endemic. Genetic polymorphisms in at least four genes are implicated in QN susceptibility, and their significance often depends on the genetic background of the parasites. In this study, we have culture-adapted 60 P. falciparum clinical isolates from the China-Myanmar border and assessed their in vitro responses to QN. Our results showed that >50% of the parasite isolates displayed reduced sensitivity to QN, with a half-maximal inhibitory concentration (IC50) above 500 nM. Genotyping of pfcrt found that an overwhelming proportion of the parasite population had the chloroquine-resistant genotype, whereas pfmdr1 mutation genotypes and gene amplification were rare. Genotyping of the P. falciparum Na+/H + exchanger gene (pfnhe1) at the minisatellite ms4760 locus identified 10 haplotypes. Haplotype 7, which harbors three copies of the DNNND repeat, was the most predominant, accounting for nearly half of the parasite isolates. Correlation studies did not reveal significant associations of the polymorphisms in pfcrt and pfmdr1 genes with QN response. However, the ms4760 haplotypes were highly associated with in vitro QN responses. In particular, parasite isolates with an increased DNNND copy number tended to have significantly reduced QN susceptibility, whereas parasite isolates with a higher NHNDNHNNDDD copy number had increased QN susceptibility. This study provided further support for the importance of pfnhe1 polymorphisms in influencing QNR in P. falciparum.

Original languageEnglish (US)
Pages (from-to)4306-4313
Number of pages8
JournalAntimicrobial agents and chemotherapy
Volume54
Issue number10
DOIs
StatePublished - Oct 1 2010

Fingerprint

Myanmar
Sodium-Hydrogen Antiporter
Quinine
Plasmodium falciparum
China
Parasites
Haplotypes
Genotype
Genes
Minisatellite Repeats
Gene Amplification
Chloroquine
Genetic Polymorphisms
Inhibitory Concentration 50
Malaria
In Vitro Techniques
Mutation
Population

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Meng, Hao ; Zhang, Rongping ; Yang, Henglin ; Fan, Qi ; Su, Xinzhuan ; Miao, Jun ; Cui, Liwang ; Yang, Zhaoqing. / In vitro sensitivity of Plasmodium falciparum clinical isolates from the China-Myanmar border area to quinine and association with polymorphism in the Na+/H+ exchanger. In: Antimicrobial agents and chemotherapy. 2010 ; Vol. 54, No. 10. pp. 4306-4313.
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abstract = "Quinine resistance (QNR) in Plasmodium falciparum has been detected in many regions of the world where malaria is endemic. Genetic polymorphisms in at least four genes are implicated in QN susceptibility, and their significance often depends on the genetic background of the parasites. In this study, we have culture-adapted 60 P. falciparum clinical isolates from the China-Myanmar border and assessed their in vitro responses to QN. Our results showed that >50{\%} of the parasite isolates displayed reduced sensitivity to QN, with a half-maximal inhibitory concentration (IC50) above 500 nM. Genotyping of pfcrt found that an overwhelming proportion of the parasite population had the chloroquine-resistant genotype, whereas pfmdr1 mutation genotypes and gene amplification were rare. Genotyping of the P. falciparum Na+/H + exchanger gene (pfnhe1) at the minisatellite ms4760 locus identified 10 haplotypes. Haplotype 7, which harbors three copies of the DNNND repeat, was the most predominant, accounting for nearly half of the parasite isolates. Correlation studies did not reveal significant associations of the polymorphisms in pfcrt and pfmdr1 genes with QN response. However, the ms4760 haplotypes were highly associated with in vitro QN responses. In particular, parasite isolates with an increased DNNND copy number tended to have significantly reduced QN susceptibility, whereas parasite isolates with a higher NHNDNHNNDDD copy number had increased QN susceptibility. This study provided further support for the importance of pfnhe1 polymorphisms in influencing QNR in P. falciparum.",
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In vitro sensitivity of Plasmodium falciparum clinical isolates from the China-Myanmar border area to quinine and association with polymorphism in the Na+/H+ exchanger. / Meng, Hao; Zhang, Rongping; Yang, Henglin; Fan, Qi; Su, Xinzhuan; Miao, Jun; Cui, Liwang; Yang, Zhaoqing.

In: Antimicrobial agents and chemotherapy, Vol. 54, No. 10, 01.10.2010, p. 4306-4313.

Research output: Contribution to journalArticle

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T1 - In vitro sensitivity of Plasmodium falciparum clinical isolates from the China-Myanmar border area to quinine and association with polymorphism in the Na+/H+ exchanger

AU - Meng, Hao

AU - Zhang, Rongping

AU - Yang, Henglin

AU - Fan, Qi

AU - Su, Xinzhuan

AU - Miao, Jun

AU - Cui, Liwang

AU - Yang, Zhaoqing

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