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尼日尔恶性疟原虫ATP酶的多态性:三种新点突变的检测

Polymorphism of PfATPase in Niger: detection of three new point mutations.

作者信息

Ibrahim Maman Laminou, Khim Nimol, Adam Hassane Hadiza, Ariey Frédéric, Duchemin Jean-Bernard

机构信息

Centre de Recherche Médicale et Sanitaire (CERMES), BP 10887 Niamey, Niger.

出版信息

Malar J. 2009 Feb 18;8:28. doi: 10.1186/1475-2875-8-28.

Abstract

BACKGROUND

Plasmodium falciparum resistance to drugs remains a major public health issue in Niger. The therapeutic failure index for chloroquine and sulphadoxine-pyrimethamine are, respectively 20% and 21.9%. In December 2005, the National Malaria Control Programme promoted the use of artemisinin combination therapy (ACT) as first-line treatment of the uncomplicated malaria cases. Recently, studies have shown a relationship between the SERCA PfATPase6 gene and artemisinin efficacy, and pointed it out as a potential molecular marker for resistance. The goal of this work was to describe the baseline polymorphism of PfATPase6 gene in Niger, at a time when the national implementation of the ACT policy had just begun.

MATERIALS AND METHODS

The DNA polymorphism of the PfATPase6 gene of 87 P. falciparum samples from Niger was analysed by sequencing. The links between the mutation occurrence and environment and human host factors were tested by bivariate analysis.

RESULTS

The P. falciparum PfATPase6 gene presented polymorphisms at codons 537, 561, 569, 630, 639, 716 levels. All the mutations found were rare, except the PfATPaseN569K found in 17.2% of samples. No associated factor has been observed.

CONCLUSION

The P. falciparum PfATPase gene is polymorphic at the 569 codon. As ACT is getting more and more used, the PfATPase6 gene polymorphism needs to be monitored in association with phenotypic - in vivo and/or in vitro - drug efficacy tests.

摘要

背景

恶性疟原虫对药物的耐药性仍是尼日尔的一个主要公共卫生问题。氯喹和磺胺多辛-乙胺嘧啶的治疗失败率分别为20%和21.9%。2005年12月,国家疟疾控制规划推广使用青蒿素联合疗法(ACT)作为非复杂性疟疾病例的一线治疗方法。最近,研究显示了SERCA PfATPase6基因与青蒿素疗效之间的关系,并指出其为一种潜在的耐药分子标记。这项工作的目的是在国家刚开始实施ACT政策时,描述尼日尔PfATPase6基因的基线多态性。

材料与方法

通过测序分析了来自尼日尔的87份恶性疟原虫样本中PfATPase6基因的DNA多态性。通过双变量分析测试了突变发生与环境及人类宿主因素之间的联系。

结果

恶性疟原虫PfATPase6基因在537、561、569、630、639、716密码子水平呈现多态性。除在17.2%的样本中发现的PfATPaseN569K外,所有发现的突变都很罕见。未观察到相关因素。

结论

恶性疟原虫PfATPase基因在569密码子处具有多态性。随着ACT的使用越来越多,需要结合表型(体内和/或体外)药物疗效测试对PfATPase6基因多态性进行监测。

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