Faculty of Medical Sciences, Department of Biochemistry, Anton de Kom Universiteit van Suriname, Kernkampweg 5, Paramaribo, Suriname.
Malar J. 2012 Sep 11;11:322. doi: 10.1186/1475-2875-11-322.
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.
PfATP6 基因内的多态性被认为是青蒿素疗效的潜在分子标志物。自 2004 年以来,青蒿素联合疗法(ACT)被用作苏里南无并发症疟疾病例的一线治疗方法。本研究旨在确定在采用 ACT 方案前后,苏里南 PfATP6 基因中多态性标记的变化情况,特别是 S769N 突变,该突变与邻国法属圭亚那的体外青蒿素耐药性有关。
使用 PCR 扩增和限制性内切酶分析,对来自苏里南的恶性疟原虫 PfATP6 基因进行了 28 个样本的检测,以评估和确定潜在的感兴趣的单核苷酸多态性的流行情况。在采用 ACT 方案前后,对来自三个流行地区的寄生虫中可能与青蒿素耐药表型相关的多态性[L263E;A623E;S769N]进行了特征描述。此外,还比较了在 ACT 控制后复发疟疾患者的配对疟原虫分离物中这些分子标记的状态。
所有研究样本在三个位置(L263、A623、S769)均表现出野生型基因型。
在采用 ACT 方案前后以及与流行地区无关的所有研究分离株均携带这三个研究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 基因突变无关,这挑战了青蒿素耐药与 PfATP6 基因中的这些突变有关的假设。