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Prevalence of <i>pvmrp1</i> Polymorphisms and Its Contribution to Antimalarial Response
oleh: Yi Yin, Gangcheng Chen, Myat Htut Nyunt, Meihua Zhang, Yaobao Liu, Guoding Zhu, Xinlong He, Fang Tian, Jun Cao, Eun-taek Han, Feng Lu
Format: | Article |
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Diterbitkan: | MDPI AG 2022-07-01 |
Deskripsi
As more sporadic cases of chloroquine resistance occur (CQR) in <i>Plasmodium vivax</i> (<i>P. vivax</i>) malaria, molecular markers have become an important tool to monitor the introduction and spread of drug resistance. <i>P. vivax</i> multidrug resistance-associated protein 1 (PvMRP1), as one of the members of the ATP-binding cassette (ABC) transporters, may modulate this phenotype. In this study, we investigated the gene mutations and copy number variations (CNVs) in the <i>pvmrp1</i> in 102 <i>P. vivax</i> isolates from China, the Republic of Korea (ROK), Myanmar, Papua New Guinea (PNG), Pakistan, the Democratic People’s Republic of Korea (PRK), and Cambodia. And we also obtained 72 available global <i>pvmrp1</i> sequences deposited in the PlasmoDB database to investigate the genetic diversity, haplotype diversity, natural selection, and population structure of <i>pvmrp1</i>. In total, 29 single nucleotide polymorphisms reflected in 23 non-synonymous, five synonymous mutations and one gene deletion were identified, and CNVs were found in 2.9% of the isolates. Combined with the antimalarial drug susceptibility observed in the previous in vitro assays, except the prevalence of S354N between the two CQ sensitivity categories revealed a significant difference, no genetic mutations or CNVs associated with drug sensitivity were found. The genetic polymorphism analysis of 166 isolates worldwide found that the overall nucleotide diversity (π) of <i>pvmrp1</i> was 0.0011, with 46 haplotypes identified (<i>Hd</i> = 0.9290). The ratio of non-synonymous to synonymous mutations (dn/ds = 0.5536) and the neutrality tests statistic Fu and Li’s D* test (Fu and Li’s D* = −3.9871, <i>p</i> < 0.02) suggests that <i>pvmrp1</i> had evolved under a purifying selection. Due to geographical differences, genetic differentiation levels of <i>pvmrp1</i> in different regions were different to some extent. Overall, this study provides a new idea for finding CQR molecular monitoring of <i>P. vivax</i> and provides more sequences of <i>pvmrp1</i> in Asia for subsequent research. However, further validation is still needed through laboratory and epidemiological field studies of <i>P. vivax</i> samples from more regions.