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01.12.2012 | Research | Ausgabe 1/2012 Open Access

Malaria Journal 1/2012

Possible association of the Plasmodium falciparum T1526C resa2 gene mutation with severe malaria

Zeitschrift:
Malaria Journal > Ausgabe 1/2012
Autoren:
Rémy Durand, Florence Migot-Nabias, Valérie Andriantsoanirina, Elise Seringe, Firmine Viwami, Gratien Sagbo, Francis Lalya, Philippe Deloron, Odile Mercereau-Puijalon, Serge Bonnefoy
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2875-11-128) contains supplementary material, which is available to authorized users.

Competing interest

The authors declare that they have no competing interest.

Authors’ contributions

RD, FMN, ES, PD, OMP and SB conceived and designed the project. FMN, FV, GS, and FL performed clinical studies. RD, FMN, VA, and SB performed experiments. RD, VA, ES, FV, GS, FL and SB analysed the data. RD and SB prepared the manuscript. FMN, OMP and PD critically reviewed the manuscript. All authors read and approved the final manuscript.

Abstract

Background

Plasmodium falciparum exports proteins that remodel the erythrocyte membrane. One such protein, called Pf155/RESA (RESA1) contributes to parasite fitness, optimizing parasite survival during febrile episodes. Resa1 gene is a member of a small family comprising three highly related genes. Preliminary evidence led to a search for clues indicating the involvement of RESA2 protein in the pathophysiology of malaria. In the present study, cDNA sequence of resa2 gene was obtained from two different strains. The proportion of P. falciparum isolates having a non-stop T1526C mutation in resa2 gene was evaluated and the association of this genotype with severity of malaria was investigated.

Methods

Resa2 cDNAs of two different strains (a patient isolate and K1 culture adapted strain) was obtained by RT-PCR and DNA sequencing was performed to confirm its gene structure. The proportion of isolates having a T1526C mutation was evaluated using a PCR-RFLP methodology on groups of severe malaria and uncomplicated patients recruited in 1991–1994 in Senegal and in 2009 in Benin.

Results

A unique ORF with an internal translation stop was found in the patient isolate (Genbank access number : JN183870), while the K1 strain harboured the T1526C mutation (Genbank access number : JN183869) which affects the internal stop codon and restores a full length coding sequence. About 14% of isolates obtained from Senegal and Benin harboured mutant T1526C parasites. Some isolates had both wild and mutant resa alleles. The analysis excluding those mixed isolates showed that the resa2 T1526C mutation was found more frequently in severe malaria cases than in uncomplicated cases (p = 0.008). The association of the presence of the mutant allele and parasitaemia >4% was shown in multivariate analysis (p = 0.03) in the group of Beninese children.

Conclusions

All T1526C mutant parasites theoretically have the ability to give rise to a full-length RESA2 protein. This study raises the hypothesis that the RESA2 protein could favour high-density infections. Other studies in various geographic settings and probably including more patients are now required to replicate these results and to answer the questions raised by these results.
Zusatzmaterial
Additional file 1: Characteristics of 39 Senegalese patients presenting with severe P. falciparum malaria. (XLS 24 KB)
12936_2012_2149_MOESM1_ESM.xls
Additional file 2: Characteristics of 30 Senegalese patients presenting with uncomplicated P. falciparum malaria. (XLS 3 MB)
12936_2012_2149_MOESM2_ESM.xls
Additional file 3: Characteristics of 54 Beninese patients presenting with severe P. falciparum malaria. (XLS 24 KB)
12936_2012_2149_MOESM3_ESM.xls
Additional file 4: Characteristics of 47 Beninese patients presenting with uncomplicated P. falciparum malaria. (XLS 28 KB)
12936_2012_2149_MOESM4_ESM.xls
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