Polymorphisms in the Plasmodium falciparum pfcrt and pfmdr-1 genes and clinical response to chloroquine in Kampala, Uganda
Polymorphisms in the Plasmodium falciparum pfcrt and pfmdr-1 genes and clinical response to chloroquine in Kampala, Uganda
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DOI：
10.1086/319865
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发表时间：
2001-05-01
影响因子：
6.4
通讯作者：
Rosenthal, PJ
中科院分区：
文献类型：
--
作者：
Dorsey, G;Kamya, MR;Rosenthal, PJ
恶性疟原虫氯喹耐药的分子机制仍不清楚。pfcrt和pfmdr-1基因的多态性与体外氯喹耐药性有关，尽管田间研究有限。在乌干达坎帕拉的无并发症疟疾患者寄生虫的已知多态性评估中，8个pfcrt突变和2个pfmdr-1突变的存在与氯喹治疗的临床反应无关。最值得注意的是，pfcrt赖氨酸苏氨酸突变在76位，最近与体外氯喹耐药性完全相关，存在于114个分离株的100%中，其中约一半来自氯喹治疗后临床恢复的患者。这些结果表明，尽管关键的pfcrt多态性可能是氯喹耐药高水平地区的氯喹耐药的必要因素，但其他因素，如宿主免疫，可能有助于临床结果。
The molecular mechanism of chloroquine resistance in Plasmodium falciparum remains uncertain. Polymorphisms in the pfcrt and pfmdr-1 genes have been associated with chloroquine resistance in vitro, although field studies are limited. In evaluations of known polymorphisms in parasites from patients with uncomplicated malaria in Kampala, Uganda, the presence of 8 pfcrt mutations and 2 pfmdr-1 mutations did not correlate with clinical response to therapy with chloroquine. Most notably, the pfcrt lysine threonine mutation at position 76, which recently correlated fully with chloroquine resistance in vitro, was present in 100% of 114 isolates, of which about half were from patients who recovered clinically after chloroquine therapy. These results suggest that, although key pfcrt polymorphisms may be necessary for the elaboration of resistance to chloroquine in areas with high levels of chloroquine resistance, other factors, such as host immunity, may contribute to clinical outcomes.