Genetic diversity of the Pvk12 gene in Plasmodium vivax from the China-Myanmar border area

Abstract

Background Plasmodium falciparum resistance to artemisinin emerged in the Greater Mekong Sub-region has been associated with mutations in the propeller domain of the kelch gene Pfk13.MethodsHere the polymorphisms in Pvk12 gene, the orthologue of Pfk13 in Plasmodium vivax, were determined by PCR and sequencing in 262 clinical isolates collected in recent years (2012–2015) from the China-Myanmar border area.ResultsSequencing of full-length Pvk12 genes from these isolates identified three synonymous mutations (N172N, S360S, S697S) and one non-synonymous mutation M124I, all of which were at very low prevalence (2.0–3.1%). Moreover, these mutations were non-overlapping between the two study sites on both sides of the border. Molecular evolutionary analysis detected signature of purifying selection on Pvk12.ConclusionsThere is no direct evidence that Pvk12 is involved in artemisinin resistance in P. vivax, but it remains a potential candidate requiring further investigation. Continuous monitoring of potential drug resistance in this parasite is needed in order to facilitate the regional malaria elimination campaign.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1592-z) contains supplementary material, which is available to authorized users.

The prevalence of molecular markers of drug resistance in Plasmodium vivax from the border regions of Thailand in 2008 and 2014

“…There appears to be selection acting on these mutations in the Greater Mekong Region, as their prevalence has increased throughout the years artemisinin has been used. The situation in P. vivax is, however, much less clear, with genetic diversity observed in the orthologous Pvk12 gene ( Popovici et al, 2015 ; Deng et al, 2016 ; Pearson et al, 2016 ; Wang et al, 2016 ).…”

“…Artemisinin resistance in P. falciparum is linked to mutations in the Kelch 13 ( Pfk13 ) gene, and high prevalences of mutant alleles have been observed in Southeast Asia ( Ashley et al, 2014 ; Menard et al, 2016 ). There are limited studies on the prevalence of mutations in the P. vivax orthologue of this gene ( Pvk12 ), although three studies that looked for polymorphisms at this locus from samples collected in Southeast Asia between 2008 and 2013 suggest that there is limited polymorphism present ( Popovici et al, 2015 ; Deng et al, 2016 ; Wang et al, 2016 ).…”

Assessment of drug resistance associated genetic diversity in Mauritanian isolates of Plasmodium vivax reveals limited polymorphism

“…In P. vivax , Pvk12 was identified as the homologous gene of Pfk13 [ 39 ]. At present, there is no molecular indication that Pvk12 undergoes a high degree of mutations as its P. falciparum homolog, even in Southeast Asia [ 39 , 58 – 60 ]. The sequence data of Mauritanian P. vivax isolates also indicate the absence of polymorphism in the Pvk12 gene fragment that was amplified and analysed.…”

Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border

“…Mutations in the propeller region of P. falciparum kelch 13 ( pfk13 ) gene are the main genetic marker for artemisinin resistance [ 41 ]. It is logical to determine whether artemisinin drugs have imposed similar selective pressure on the pfk13 ortholog on chromosome 12 of P. vivax ( pvk12) [ 42 – 44 ].…”