Polymorphism of Plasmodium falciparum Na+/H+ exchanger is indicative of a low in vitro quinine susceptibility in isolates from Viet Nam View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-06-14

AUTHORS

Véronique Sinou, Le Hong Quang, Stéphane Pelleau, Vu Nhu Huong, Nguyen Thu Huong, Le Minh Tai, Lionel Bertaux, Marc Desbordes, Christine Latour, Lai Quang Long, Nguyen Xuan Thanh, Daniel Parzy

ABSTRACT

BackgroundThe Plasmodium falciparum NA+/H+ exchanger (pfnhe1, gene PF13_0019) has recently been proposed to influence quinine (QN) susceptibility. However, its contribution to QN resistance seems to vary geographically depending on the genetic background of the parasites. Here, the role of this gene was investigated in in vitro QN susceptibility of isolates from Viet Nam.MethodNinety-eight isolates were obtained from three different regions of the Binh Phuoc and Dak Nong bordering Cambodia provinces during 2006-2008. Among these, 79 were identified as monoclonal infection and were genotyped at the microsatellite pfnhe1 ms4760 locus and in vitro QN sensitivity data were obtained for 51 isolates. Parasite growth was assessed in the field using the HRP2 immunodetection assay.ResultsSignificant associations were found between polymorphisms at pfnhe1 microsatellite ms4760 and susceptibility to QN. Isolates with two or more DNNND exhibited much lower susceptibility to QN than those harbouring zero or one DNNND repeats (median IC50 of 682 nM versus median IC50 of 300 nM; p = 0.0146) while isolates with one NHNDNHNNDDD repeat presented significantly reduced QN susceptibility than those who had two (median IC50 of 704 nM versus median IC50 of 375 nM; p < 0.01). These QNR associated genotype features were mainly due to the over representation of profile 7 among isolates (76.5%). The majority of parasites had pfcrt76T and wild-type pfmdr1 (> 95%) thus preventing analysis of associations with these mutations. Interestingly, area with the highest median QN IC50 showed also the highest percentage of isolates carrying the pfnhe1 haplotype 7.ConclusionsThe haplotype 7 which is the typical Asian profile is likely well-adapted to high drug pressure in this area and may constitute a good genetic marker to evaluate the dissemination of QNR in this part of the world. More... »

PAGES

164

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1475-2875-10-164

DOI

http://dx.doi.org/10.1186/1475-2875-10-164

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1026269826

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21669011


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29 DNNND repeats
30 Dak Nong
31 IC50
32 NHNDNHNNDDD repeats
33 Nam
34 Nong
35 Phuoc
36 Plasmodium falciparum
37 Province
38 QN resistance
39 QN susceptibility
40 Qn
41 ResultsSignificant associations
42 Viet Nam
43 analysis
44 analysis of association
45 area
46 assays
47 association
48 background
49 contribution
50 data
51 different regions
52 dissemination
53 drug pressure
54 exchanger
55 falciparum
56 features
57 field
58 genes
59 genetic background
60 genetic markers
61 genotype features
62 good genetic marker
63 growth
64 haplotype 7
65 high drug pressure
66 high percentage
67 immunodetection assays
68 infection
69 isolates
70 loci
71 low susceptibility
72 majority
73 majority of parasites
74 markers
75 monoclonal infections
76 mutations
77 over representation
78 parasite growth
79 parasites
80 part
81 percentage
82 pfmdr1
83 polymorphism
84 pressure
85 profile
86 profile 7
87 qnrS
88 quinine susceptibility
89 region
90 repeats
91 representation
92 resistance
93 role
94 sensitivity data
95 susceptibility
96 wild-type Pfmdr1
97 world
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