The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin
The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin
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DOI：
10.1016/s0166-6851(00)00201-2
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发表时间：
2000-04-30
影响因子：
1.5
通讯作者：
Warhurst, DC
中科院分区：
文献类型：
--
作者：
Duraisingh, MT;Jones, P;Warhurst, DC
虽然恶性疟原虫的氯喹耐药性（CQR）正在增加，并已报告对其他抗疟药物的抗药性，但其分子基础仍不清楚。在这项研究中，从冈比亚（一个新兴的CQR地区）获得了新鲜的田间分离株，并测试了对抗疟疾药物甲氟喹、卤泛群、青蒿素、双氢青蒿素、氯喹和奎宁的敏感性。使用基于PCR的系统评估pfmdr 1基因的序列多态性和cg 2基因的大小多态性。在pfmdr 1的tyr-86等位基因的存在与甲氟喹和卤泛群敏感性增加之间观察到强关联。以及结构无关的药物青蒿素和双氢青蒿素。一个较弱的关联被发现之间的存在tyr-86和氯喹和奎宁的耐药性增加。Cg 2 Dd 2-like omega repeal size多态性与氯喹耐药性增加和甲氟喹和卤泛群敏感性增加相关。基因内关联也被发现之间的多态性在聚天冬酰胺连接区的pfmdr 1和tyr-86等位基因，这可能是由于遗传搭便车，指示最近的选择氯喹。我们的数据支持一个假设，其中pfmdr 1基因赋予一个真正的多药耐药表型，这是失去了突变。(C)2000 Elsevier Science B. V.保留所有权利。
Although chloroquine-resistance (CQR) in Plasmodium falciparum is increasing and resistance to other blood schizonticidal anti-malarials has been reported, the molecular basis remains unclear. In this study fresh field isolates were obtained from The Gambia, an area of emerging CQR and tested for sensitivity to the anti-malarial drugs mefloquine, halofantrine, artemisinin, dihydroartemisinin, chloroquine and quinine. Sequence polymorphisms in the pfmdr 1 gene and size polymorphisms in the cg2 gene were assessed using PCR-based systems. A strong association was observed between the presence of the tyr-86 allele of pfmdr 1 and increased sensitivity to mefloquine and halofantrine. as well as the structurally unrelated drugs artemisinin and dihydroartemisinin. A weaker association was found between the presence of tyr-86 and increased resistance to chloroquine and quinine. The cg2 Dd2-like omega repeal size polymorphism was associated with increased resistance to chloroquine and increased sensitivity to mefloquine and halofantrine. An intragenic association was also found between a polymorphism in the polyasparagine linker region of pfmdr 1 and the tyr-86 allele, which may be due to genetic hitchhiking, indicative of recent selection by chloroquine. Our data support a hypothesis where the pfmdr 1 gene confers a true multidrug resistance phenotype which is lost by mutation. (C) 2000 Elsevier Science B.V. All rights reserved.