Mita Toshihiro, Kaneko Akira, Hombhanje Francis, Hwaihwanje Ilomo, Takahashi Nobuyuki, Osawa Hikota, Tsukahara Takahiro, Masta Andrew, Lum Jeffery K, Kobayakawa Takatoshi, Ishizaki Takashi, Björkman Anders
Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, Tokyo 162-8666, Japan.
Acta Trop. 2006 May;98(2):137-44. doi: 10.1016/j.actatropica.2006.03.002. Epub 2006 Apr 18.
The N86Y mutation in pfmdr1 is reported to play an additional role for the chloroquine resistance in Plasmodium falciparum isolates. However, not much has been done to clarify whether this mutation augments the level of chloroquine resistance in the isolates harboring pfcrt K76T mutation. We compared the in vitro chloroquine efficacy between pfcrt K76T mutant parasites with or without N86Y mutation from Papua New Guinea. A total of 57 isolates (4% sensitive, 14% borderline, and 82% resistant) were successfully tested in vitro for chloroquine sensitivity. We found a slightly higher effective concentration of chloroquine needed to inhibit P. falciparum by 50% (mean EC50=107 nM) in isolates with the pfcrt K76T+pfmdr1 N86Y than that in isolates with the pfcrt K76T+pfmdr1 N86 (EC50=88 nM), but this difference was not statistically significant. A significant non-random association was observed between the pfcrt K76T and pfmdr1 N86Y alleles. Our results suggest that the pfmdr1 N86Y mutation plays a compensatory role to chloroquine-resistant isolates under a chloroquine pressure while it may also augment the level of chloroquine resistance in the K76T parasites to a small extent.
据报道，恶性疟原虫分离株中pfmdr1基因的N86Y突变在氯喹耐药性方面发挥了额外作用。然而，关于该突变是否会增强携带pfcrt K76T突变的分离株的氯喹耐药水平，尚未开展太多研究。我们比较了来自巴布亚新几内亚的携带或不携带N86Y突变的pfcrt K76T突变疟原虫的体外氯喹疗效。共有57株分离株（4%敏感、14%临界和82%耐药）成功进行了体外氯喹敏感性测试。我们发现，携带pfcrt K76T + pfmdr1 N86Y的分离株中，抑制恶性疟原虫50%所需的氯喹有效浓度略高于携带pfcrt K76T + pfmdr1 N86的分离株（平均EC50 = 107 nM，后者为EC50 = 88 nM），但这种差异无统计学意义。在pfcrt K76T和pfmdr1 N86Y等位基因之间观察到显著的非随机关联。我们的结果表明，在氯喹压力下，pfmdr1 N86Y突变对氯喹耐药分离株起补偿作用，同时它也可能在一定程度上增强K76T疟原虫的氯喹耐药水平。
