| Summary: | <p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum</it> exports proteins that remodel the erythrocyte membrane. One such protein, called Pf155/RESA (RESA1) contributes to parasite fitness, optimizing parasite survival during febrile episodes. <it>Resa1</it> 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 <it>resa2</it> gene was obtained from two different strains. The proportion of <it>P. falciparum</it> isolates having a non-stop T1526C mutation in <it>resa2</it> gene was evaluated and the association of this genotype with severity of malaria was investigated.</p> <p>Methods</p> <p><it>Resa2</it> 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.</p> <p>Results</p> <p>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 <it>resa</it> alleles. The analysis excluding those mixed isolates showed that the <it>resa2</it> 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.</p> <p>Conclusions</p> <p>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.</p>
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