SEVERAL ALLELES OF THE MULTIDRUG-RESISTANCE GENE ARE CLOSELY LINKED TO CHLOROQUINE RESISTANCE IN PLASMODIUM-FALCIPARUM

被引：526

作者：

FOOTE, SJ ^{[1
]}

KYLE, DE ^{[1
]}

MARTIN, RK ^{[1
]}

ODUOLA, AMJ ^{[1
]}

FORSYTH, K ^{[1
]}

KEMP, DJ ^{[1
]}

COWMAN, AF ^{[1
]}

机构：

[1] WALTER REED ARMY MED CTR,WASHINGTON,DC 20307

来源：

NATURE | 1990年 / 345卷 / 6272期

关键词：

D O I：

10.1038/345255a0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

THE lethal form of human malaria caused by Plasmodium falciparum is virtually uncontrollable in many areas because of the development of drug resistance, in particular chloroquine resistance (CQR). CQR is biologically similar to the multiple drug resistance phenotype (MDR) of mammalian tumour cells, as both involve expulsion of drug from the cell and both can be reversed by calcium channel antagonists1. A homologue (pfmdr1) of the mammalian multidrug resistance gene has been implicated in CQR because it is amplified in some CQR isolates of P. falciparum2,3 as is an mdr gene in MDR tumour cells4. We show here that the complete sequences of pfmdr1 genes from 2 CQ sensitive (CQS) P. falciparum isolates are identical. In 5 CQR isolates, 1-4 key nucleotide differences resulted in amino acid substitutions. On the basis of these substitutions, we have correctly predicted the CQS/CQR status of a further 34 out of 36 isolates. This is a paradox as CQR arises much less frequently than would be predicted if single point mutations were sufficient. We conclude that a mutated pfmdr1 gene is one of at least two mutated genes required for CQR. © 1990 Nature Publishing Group.

引用

页码：255 / 258

页数：4

共 16 条

[1] AN ALTERED PATTERN OF CROSS-RESISTANCE IN MULTIDRUG-RESISTANT HUMAN-CELLS RESULTS FROM SPONTANEOUS MUTATIONS IN THE MDR1 (P-GLYCOPROTEIN) GENE [J].