The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa
The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa
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DOI：
10.1111/j.1365-3156.2007.01843.x
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发表时间：
2007-06-01
影响因子：
3.3
通讯作者：
Gil, Jose P.
中科院分区：
文献类型：
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作者：
Sisowath, Christin;Ferreira, Pedro E.;Gil, Jose P.
目的青蒿素-甲氨芳碱（AL）是目前在非洲最受欢迎的治疗非复杂性恶性疟原虫疟疾的联合疗法，最近显示出对pfmdr186n等位基因的选择性。本研究的目的是寻找其他可能参与蒿甲醚-芴嘧啶耐受性和/或耐药的突变，即pfmdr1基因扩增、pfmdr1 Y184F、S1034C、N1042D、D1246Y、pfcrt S163R和PfATP6 S769N。方法采用PCR-限制性内切片段长度多态性和实时荧光定量PCR扩增技术对桑给巴尔200例单纯恶性疟原虫AL患儿寄生虫的上述snp进行分析。结果治疗后再感染中pfmdr1 184F多与86N合用，差异有统计学意义。未发现pfmdr1基因扩增。结论不同的pfmdr1等位基因参与了对氟苯曲明的耐受/耐药过程。
Objective Artemether-lumefantrine (AL), presently the most favoured combination therapy against uncomplicated Plasmodium falciparum malaria in Africa, has recently shown to select for the pfmdr1 86N allele. The objective of this study was to search for the selection of other mutations potentially involved in artemether-lumefantrine tolerance and/or resistance, i.e. pfmdr1 gene amplification, pfmdr1 Y184F, S1034C, N1042D, D1246Y, pfcrt S163R and PfATP6 S769N.Methods The above mentioned SNPs were analysed by PCR-restriction fragment length polymorphism and pfmdr1 gene amplification by real-time PCR based protocols in parasites from 200 children treated with AL for uncomplicated P. falciparum malaria in Zanzibar.Results A statistically significant selection of pfmdr1 184F mostly in combination with 86N was seen in reinfections after treatment. No pfmdr1 gene amplification was found.Conclusion The results suggest that different pfmdr1 alleles are involved in the development of tolerance/resistance to lumefantrine.