Sisowath Christin, Ferreira Pedro E, Bustamante Leyla Y, Dahlström Sabina, Mårtensson Andreas, Björkman Anders, Krishna Sanjeev, Gil José P
Malaria Research Unit, Division of Infectious Diseases, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Trop Med Int Health. 2007 Jun;12(6):736-42. doi: 10.1111/j.1365-3156.2007.01843.x.
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.
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.
A statistically significant selection of pfmdr1 184F mostly in combination with 86N was seen in reinfections after treatment. No pfmdr1 gene amplification was found.
The results suggest that different pfmdr1 alleles are involved in the development of tolerance/resistance to lumefantrine.
蒿甲醚-本芴醇（AL）是目前非洲治疗非复杂性恶性疟原虫疟疾最常用的联合疗法，最近研究表明其会选择pfmdr1 86N等位基因。本研究的目的是寻找其他可能与蒿甲醚-本芴醇耐受性和/或抗性有关的突变，即pfmdr1基因扩增、pfmdr1 Y184F、S1034C、N1042D、D1246Y、pfcrt S163R和PfATP6 S769N。
采用聚合酶链反应-限制性片段长度多态性分析上述单核苷酸多态性，并通过基于实时聚合酶链反应的方法对来自桑给巴尔200名接受蒿甲醚-本芴醇治疗非复杂性恶性疟原虫疟疾儿童的寄生虫进行pfmdr1基因扩增分析。
治疗后再感染中观察到pfmdr1 184F有统计学意义的选择，大多与86N同时出现。未发现pfmdr1基因扩增。
结果表明不同的pfmdr1等位基因与本芴醇耐受性/抗性的发展有关。
