Unité de Parasitologie, Unité Mixte de Recherche 6236, Institut de Recherche Biomédicale des Armées-Antenne de Marseille, Marseille, France.
Malar J. 2011 Feb 11;10:37. doi: 10.1186/1475-2875-10-37.
Quinine is still recommended as an effective therapy for severe cases of Plasmodium falciparum malaria, but the parasite has developed resistance to the drug in some cases. Investigations into the genetic basis for quinine resistance (QNR) suggest that QNR is complex and involves several genes, with either an additive or a pairwise effect. The results obtained when assessing one of these genes, the plasmodial Na+/H+ exchanger, Pfnhe-1, were found to depend upon the geographic origin of the parasite strain. Most of the associations identified have been made in Asian strains; in contrast, in African strains, the influence of Pfnhe on QNR is not apparent. However, a recent study carried out in Kenya did show a significant association between a Pfnhe polymorphism and QNR. As genetic differences may exist across the African continent, more field data are needed to determine if this association exists in other African regions. In the present study, association between Pfnhe and QNR is investigated in a series of isolates from central Africa.
The sequence analysis of the polymorphisms at the Pfnhe-1 ms4760 microsatellite and the evaluation of in vitro quinine susceptibility (by isotopic assay) were conducted in 74 P. falciparum isolates from the Republic of Congo.
Polymorphisms in the number of DNNND or NHNDNHNNDDD repeats in the Pfnhe-1 ms4760 microsatellite were not associated with quinine susceptibility.
The polymorphism in the microsatellite ms4760 in Pfnhe-1 that cannot be used to monitor quinine response in the regions of the Republic of Congo, where the isolates came from. This finding suggests that there exists a genetic background associated with geographic area for the association that will prevent the use of Pfnhe as a molecular marker for QNR. The contribution of Pfnhe to the in vitro response to quinine remains to be assessed in other regions, including in countries with different levels of drug pressure.
奎宁仍然被推荐作为治疗恶性疟原虫疟疾的有效疗法，但在某些情况下寄生虫已经对该药物产生了耐药性。对奎宁耐药性（QNR）的遗传基础的研究表明，QNR 很复杂，涉及几个基因，具有加性或成对作用。在评估其中一个基因（疟原虫 Na+/H+交换蛋白，Pfnhe-1）时获得的结果发现，该基因依赖于寄生虫株的地理起源。已确定的大多数关联都是在亚洲株中发现的；相比之下，在非洲株中，Pfnhe 对 QNR 的影响并不明显。然而，最近在肯尼亚进行的一项研究确实表明，Pfnhe 多态性与 QNR 之间存在显著关联。由于遗传差异可能存在于整个非洲大陆，因此需要更多的现场数据来确定这种关联是否存在于其他非洲地区。在本研究中，对来自中非的一系列分离株进行了 Pfnhe 与 QNR 之间的关联研究。
对 74 株来自刚果共和国的恶性疟原虫分离株中的 Pfnhe-1 ms4760 微卫星的多态性进行序列分析，并通过同位素测定法评估体外奎宁敏感性。
Pfnhe-1 ms4760 微卫星中 DNNND 或 NHNDNHNNDDD 重复数的多态性与奎宁敏感性无关。
无法使用 Pfnhe-1 微卫星 ms4760 中的多态性来监测来自刚果共和国的分离株所在地区的奎宁反应。这一发现表明，存在与地理区域相关的遗传背景与关联，这将阻止使用 Pfnhe 作为 QNR 的分子标记。在其他地区，包括药物压力不同的国家，仍需要评估 Pfnhe 对奎宁体外反应的贡献。
