一项研究发现了与青蒿素耐药性有关的4个恶性疟原虫的遗传位点。大多数疟疾流行的国家在联合疗法中使用青蒿素作为治疗恶性疟原虫的一线疗法。Christopher V. Plowe及其同事对从最近出现了对青蒿素耐药的恶性疟原虫的柬埔寨西部、孟加拉国和泰国进行的青蒿素疗法有效性临床试验中收集的恶性疟原虫DNA的8079个单核苷酸多态（SNPs）——这是一种遗传变异的形式——进行了遗传分型。这组作者报告说，与来自孟加拉国的病人相比，来自柬埔寨西部的大多数接受青蒿素治疗的病人的疟原虫清除被严重延迟了，而泰国的病人表现出了一种混合的响应。这组作者发现4个单核苷酸多态（SNPs）——有两个分别在10号和14号染色体，另外两个在13号染色体上——与疟原虫清除的延迟有显着联系。在10号和13号染色体上的这些单核苷酸多态（SNPs）位于或者靠近参与一个DNA损伤耐受路径的基因，这种路径可能因为抗疟药物治疗而被激活。这组作者说，在10号染色体上的一个单核苷酸多态（SNPs）和在13号染色体上的一个单核苷酸多态（SNPs）可能作为疟原虫清除延迟的分子标记，而且可能用于监测东南亚的青蒿素耐药性。(生物谷Bioon.com)
doi: 10.1073/pnas.1211205110
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Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia
, Olivo Miottod,e,2, Arjen M. Dondorpe, Mark M. Fukudaf, Francois Nostene,g, Harald Noedlh, Mallika Imwongi, Delia Bethellf, Youry Sej, Chanthap Lonj, Stuart D. Tynerf, David L. Saundersf, Duong Socheatk, Frederic Arieyl, Aung Pyae Phyoe,g, Peter Starzengruberh, Hans-Peter Fuehrerh, Paul Swobodah, Kasia Stepniewskam, Jennifer Fleggm, Cesar Arzen, Gustavo C. Cerqueiran, Joana C. Silvan, Stacy M. Ricklefso, Stephen F. Porcellao, Robert M. Stephensp, Matthew Adamsa, Leo J. Kenefica, Susana Campinod,q, Sarah Auburnq, Bronwyn MacInnisd,q, Dominic P. Kwiatkowskid,q, Xin-zhuan Sur, Nicholas J. Whitee, Pascal Ringwalds, and Christopher V. Plowea,3
The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia.
