Genetic polymorphism in pvmdr1 and pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries

• Published in: Acta tropica 2011-02, Vol.117 (2), p.69-75
• Main Authors: Lu, Feng, Lim, Chae Seung, Nam, Deok-Hwa, Kim, Kwonkee, Lin, Khin, Kim, Tong-Soo, Lee, Hyeong-Woo, Chen, Jun-Hu, Wang, Yue, Sattabongkot, Jetsumon, Han, Eun-Taek
• Format: Article
• Language: English
• Subjects: amino acids; Animals; Antimalarials - pharmacology; Biological and medical sciences; chloroquine; Copy number; DNA Primers; Drug resistance gene; Drug Resistance, Multiple - genetics; exons; General aspects; genes; genetic polymorphism; Human protozoal diseases; Humans; In vitro drug susceptibility; Infectious diseases; Malaria; Malaria, Vivax - blood; Malaria, Vivax - drug therapy; Malaria, Vivax - parasitology; Medical sciences; Membrane Transport Proteins - genetics; Multidrug Resistance-Associated Proteins - genetics; Myanmar; Papua New Guinea; Parasitic diseases; Plasmodium vivax; Plasmodium vivax - drug effects; Plasmodium vivax - genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide - genetics; Protozoal diseases; Protozoan Proteins - genetics; pvcrt-o; pvmdr1; Republic of Korea; resistance mechanisms; Single nucleotide polymorphisms (SNPs); Thailand
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/j.actatropica.2010.08.011

Drug resistance gene polymorphisms and copy number variation of P. vivax Southeast Asian countries isolates were observed and key point mutations in two genes and isolates susceptible to high drug doses as determined by in vitro susceptibility were not found in Korean isolates. [Display omitted] ▶ Gene polymorphisms and copy number variation of pvmdr1 and pvcrt-o among isolates of P. vivax from Southeast Asian countries were observed. ▶ In Korean isolates, polymorphism of pvmdr1 was limited to the F1076L variant. ▶ No Korean isolates with high level of resistance were found by in vitro susceptibility determinations. Treatment failure of chloroquine for Plasmodium vivax infection has increased in endemic countries. However, the molecular mechanisms for resistance and in vitro susceptibility of P. vivax to chloroquine remain elusive. We investigated the prevalence of mutations in the pvmdr1 and pvcrt-o genes, and the copy number of the pvmdr1 gene in isolates from the Republic of Korea (ROK), Thailand, the Union of Myanmar (Myanmar), and Papua New Guinea (PNG). We also measured in vitro susceptibility of Korean isolates to antimalarial drugs. The pvmdr1 analysis showed that mutations at amino acid position Y976F of pvmdr1 were found in isolates from Thailand (17.9%), Myanmar (13.3%), and PNG (100%), but none from the ROK, and mutation at position F1076L was present in isolates from the ROK (100%), Thailand (60.7%), and Myanmar (46.7%). One copy of the pvmdr1 gene was observed in most isolates and double copy numbers of the gene were observed in two Thai isolates. In the exons of the pvcrt-o gene that were sequenced, a K10 insertion was present in isolates from Thailand (56.0%) and Myanmar (46.2%), and the wild type was found in all Korean isolates. The results suggest that gene polymorphisms and copy number variation was observed in isolates of P. vivax from Southeast Asian countries. In Korean isolates polymorphism as limited to the F1076L variant, and no isolates with high level of resistance were found by in vitro susceptibility determinations. Moreover, our results provide a baseline for future prospective drug studies in malaria-endemic areas.