Status of potential PfATP6 molecular markers for artemisinin resistance in Suriname.
Status of potential PfATP6 molecular markers for artemisinin resistance in Suriname.
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DOI：
10.1186/1475-2875-11-322
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发表时间：
2012-09-11
期刊：
影响因子：
3
通讯作者：
Vreden SG
中科院分区：
文献类型：
--
作者：
Adhin MR;Labadie-Bracho M;Vreden SG
PfATP6 基因内的多态性已被表明是青蒿素功效的潜在分子标记。自2004年以来，苏里南开始使用青蒿素联合疗法（ACT）作为无并发症疟疾病例的一线治疗。本研究的目的是确定苏里南在采用 ACT 方案前后 PfATP6 基因多态性标记状态的变化，特别是 S769N 突变，据报道，该突变与邻国法属圭亚那的体外蒿甲醚耐药性有关。使用 PCR 扩增和限制性酶分析对苏里南恶性疟原虫寄生虫的 PfATP6 基因进行了研究，以评估和确定潜在有趣的单核苷酸多态性的流行率。多态性[L263E； A623E； S769N]，可能与青蒿素耐药表型相关，在采用 ACT 方案之前和之后的三个流行地区的寄生虫中进行了表征。此外，在控制性 ACT 后，对来自复发性疟疾患者的配对恶性疟原虫分离株中这些分子标记的状态进行了比较。所有研究的样品在所有三个位置均表现出野生型基因型； L263、A623、S769。在采用 ACT 方案之前和之后且独立于流行区域的所有调查分离株都含有三种调查多态性的野生型基因型。该研究表明，青蒿素敏感性降低可能与 PfATP6 突变无关，这对青蒿素耐药性与 PfATP6 基因的这些突变有关的假设提出了挑战。
Polymorphisms within the PfATP6 gene have been indicated as potential molecular markers for artemisinin efficacy. Since 2004, the use of artemisinin combination therapy (ACT) was introduced as first-line treatment of the uncomplicated malaria cases in Suriname. The aim of this research was to determine changes in Suriname in the status of the polymorphic markers in the PfATP6 gene before and after the adoption of the ACT-regimen, particularly of the S769N mutation, which was reported to be associated with in vitro Artemether resistance in the neighboring country French Guiana. The PfATP6 gene from Plasmodium falciparum parasites in Suriname was investigated in 28 samples using PCR amplification and restriction enzyme analysis, to assess and determine the prevalence of potentially interesting single nucleotide polymorphisms. The polymorphisms [L263E; A623E; S769N], which may be associated with the artemisinin resistant phenotype were characterized in parasites from three endemic regions before and after the adoption of the ACT-regimen. In addition, the status of these molecular markers was compared in paired P. falciparum isolates from patients with recurring malaria after controlled ACT. All the investigated samples exhibit the wild-type genotype at all three positions; L263, A623, S769. All investigated isolates before and after the adoption of the ACT-regimen and independent of endemic region harbored the wild-type genotype for the three investigated polymorphisms. The study revealed that decreased artemisinin susceptibility could occur independent from PfATP6 mutations, challenging the assumption that artemisinin resistance is associated with these mutations in the PfATP6 gene.
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