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在实施基于青蒿素的联合疗法之前,从赤道几内亚的样本中鉴定恶性疟原虫肌浆/内质网 Ca2+-ATP 酶基因。

Characterization of the Plasmodium falciparum sarcoplasmic/endoplasmic reticulum Ca2+-ATPase gene in samples from Equatorial Guinea before implementation of artemisinin-based combination therapy.

出版信息

Am J Trop Med Hyg. 2013 Jan;88(1):43-47. doi: 10.4269/ajtmh.2012.12-0364. Epub 2012 Nov 26.

DOI:10.4269/ajtmh.2012.12-0364
PMID:23185077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3541744/
Abstract

Plasmodium falciparum resistance to the primary drugs used for treatment of malaria has become the main obstacle to malaria control. Artemisinin combination therapies are the current treatment strategy, and it has been suggested that resistance to artemisinin derivatives may be related to mutations in the Plasmodium falciparum sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase ortholog of the mammalian sarco-endoplasmic reticulum Ca(2+) ATPase gene, known as the pfatp6 gene. Thus, the purpose of this study was to determine the prevalence of single-nucleotide polymorphisms (SNPs) in pfatp6. The presence of different SNPs was detected by polymerase chain reaction amplification of the pfatp6 gene, and then sequencing to identify all possible alleles of the gene. A total of 20 SNPs were detected, including eight SNPs that have not been previously described: K481R in Malabo; R801H on Annobon Island; and the synonymous SNPs a141t, c1788t, a2211g, t2739g, a2760c, and g2836a. The genotypic profile of pfatp6 in samples from Equatorial Guinea, may be a useful epidemiologic tool for monitoring local efficacy of artemisinin combination therapies.

摘要

疟原虫对用于治疗疟疾的主要药物的耐药性已成为疟疾控制的主要障碍。青蒿素联合疗法是目前的治疗策略,有人认为对青蒿素衍生物的耐药性可能与疟原虫肌浆内质网 Ca(2+) -ATP 酶的哺乳动物肌浆内质网 Ca(2+) ATP 酶基因的同源物(称为 pfATP6 基因)的突变有关。因此,本研究旨在确定 pfATP6 中单核苷酸多态性(SNP)的流行情况。通过聚合酶链反应扩增 pfATP6 基因来检测不同 SNP 的存在,然后进行测序以鉴定基因的所有可能等位基因。共检测到 20 个 SNP,包括以前未描述的 8 个 SNP:在马拉博的 K481R;在安诺本岛的 R801H;以及同义 SNP a141t、c1788t、a2211g、t2739g、a2760c 和 g2836a。来自赤道几内亚的样本中 pfATP6 的基因型谱可能是监测当地青蒿素联合疗法疗效的有用流行病学工具。

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