The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand
The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand
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DOI：
10.1128/aac.43.12.2943
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发表时间：
1999-12-01
影响因子：
4.9
通讯作者：
Krishna, S
中科院分区：
文献类型：
--
作者：
Price, RN;Cassar, C;Krishna, S
在泰国西部边境，恶性疟原虫已对几乎所有抗疟药产生抗药性。在这些寄生虫种群的耐药性的分子基础还没有得到很好的表征。本研究评估了从泰国西部边境收集的54种寄生虫中pfmdr 1基因的遗传多态性，以确定pfmdr 1拷贝数和密码子突变与寄生虫对甲氟喹、氯喹、卤泛群、奎宁和青蒿琥酯体外敏感性的关系。密码子86处的点突变（导致Asn变为Tyr）与甲氟喹显著较低的50%抑制浓度（IC 50）相关（中位数，9 ng/ml vs 52.4 ng/ml; P = 0.003）。总的来说，35%的分离株（54个中的19个）pfmdr 1拷贝数增加，所有19个都在密码子86处携带野生型等位基因。pfmdr 1拷贝数的增加与甲氟喹（P = 0.04）和青蒿琥酯（P = 0.005）的IC（50）较高相关，与密码子86的多态性无关。pfmdr 1和结构上不同的抗疟药的耐药性之间的关系证实了真正的多药耐药表型的存在。
On the western border of Thailand, Plasmodium falciparum has become resistant to almost all antimalarial agents. The molecular basis of resistance in these parasite populations has not been well characterized. This study assessed genetic polymorphisms in the pfmdr1 gene in 54 parasites collected from the western border of Thailand to determine the relationship of pfmdr1 copy number and codon mutations with parasite sensitivities to mefloquine, chloroquine, halofantrine, quinine, and artesunate assessed in vitro. A point mutation at codon 86 (resulting in a change of Asn to Tyr) was associated with a significantly lower 50% inhibitory concentration (IC50) of mefloquine (median, 9 ng/ml versus 52.4 ng/ml; P = 0.003). Overall 35% of the isolates (19 of 54) had an increase in pfmdr1 copy number, and all 19 carried the wild-type allele at codon 86. Increased pfmdr1 copy number was associated with higher IC(50)s of mefloquine (P = 0.04) and artesunate (P = 0.005), independent of polymorphism at codon 86. The relationship between pfmdr1 and resistance to structurally distinct antimalarial agents confirms the presence of a true multidrug-resistant phenotype.