Plasmodium falciparum multidrug resistance protein 1 (pfmrp1) gene and its association with in vitro drug susceptibility of parasite isolates from north-east Myanmar
Plasmodium falciparum multidrug resistance protein 1 (pfmrp1) gene and its association with in vitro drug susceptibility of parasite isolates from north-east Myanmar
复制标题
恶性疟原虫多药耐药蛋白1（pfmrp1）基因及其与缅甸东北部疟原虫体外药物敏感性的关系
DOI：
10.1093/jac/dku125
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发表时间：
2014-08-01
影响因子：
5.2
通讯作者：
Yang, Zhaoqing
中科院分区：
文献类型：
--
作者：
Gupta, Bhavna;Xu, Shuhui;Yang, Zhaoqing
恶性疟原虫多药耐药蛋白1（pfmrp 1）最近成为一个重要的决定因素的药物耐药性和基因突变已与几种药物。本研究的目的是了解pfmrp 1基因的遗传多样性水平，并确定不同的突变与恶性疟原虫药物敏感性改变的关联，我们分析了来自东南亚，西亚，非洲，大洋洲和南美洲的193个pfmrp 1序列。我们测量了遗传多样性的水平，并确定了基因选择的特征。测定了缅甸东北部28个恶性疟原虫分离株对一组7种常用抗疟药的体外敏感性。结果在193条基因序列中共发现28个单核苷酸多态性位点，其中22个为非同义突变。虽然pfmrp 1基因的突变在同一个大陆的不同国家之间是保守的，但在不同大陆之间却不同。在缅甸东北部分离株中发现了7种非同义突变;所有这些突变在该地区以及其他邻国都相对频繁。分子进化分析检测到该基因的正选择特征。此外，在这个基因中的一些突变被发现与氯喹，甲氟喹，咯萘啶和lumefantrine.Evidence的正选择pmfrp 1和它的关联与pmfrp 1的pmfrp 1，pmfrp 1的p
Plasmodium falciparum multidrug resistance protein 1 (pfmrp1) has recently emerged as an important determinant of drug resistance and mutations in the gene have been associated with several drugs. The aim of this study was to understand the level of genetic diversity in pfmrp1 and to determine the association of different mutations with altered drug susceptibilities of P. falciparum.We analysed 193 sequences of pfmrp1 from South-East Asia, west Asia, Africa, Oceania and South America. We measured the level of genetic diversity and determined signatures of selection on the gene. In vitro susceptibilities of 28 P. falciparum isolates from north-east Myanmar to a panel of seven commonly used antimalarials were determined. Statistical analysis was performed to determine the association of different mutations with in vitro drug susceptibilities.A total of 28 single nucleotide polymorphisms were identified in 193 sequences, of which 22 were non-synonymous. Whereas mutations in the pfmrp1 gene were conserved among different countries within a continent, they were different between continents. Seven non-synonymous mutations were identified in the north-east Myanmar isolates; all were relatively frequent in this region as well as in other neighbouring countries. Molecular evolutionary analysis detected signatures of positive selection on the gene. Moreover, some mutations in this gene were found to be associated with reduced susceptibilities to chloroquine, mefloquine, pyronaridine and lumefantrine.Evidence of the positive selection of pmfrp1 and its association with the susceptibilities of parasites to multiple drugs signifies its potential as an important candidate for monitoring drug resistance.