Analysis of the key pfcrt point mutation and in vitro and in vivo response to chloroquine in Yaounde', Cameroon

Analysis of the key pfcrt point mutation and in vitro and in vivo response to chloroquine in Yaounde', Cameroon
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DOI:
10.1086/320726
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发表时间:
2001-06-15
影响因子:
6.4
通讯作者:
Ringwald, P
Ringwald, P
中科院分区:
医学2区
文献类型:
--
作者:
Basco, LK;Ringwald, P

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采用聚合酶链反应-限制性片段长度多态性技术,对111株恶性疟原虫氯喹抗性基因pfcrt的关键密码子(敏感疟原虫为Lys-76,抗性疟原虫为Thr-76)进行了分析,并与体内、体外对氯喹的反应进行了比较。关键密码子与体内(92%敏感性和76%特异性)和体外(97%敏感性和81%特异性)反应显著相关(P <0.001)。一些不一致的结果是由于多克隆感染。pfcrt多态性和表型之间的高度相关性,但并不完美,这意味着pfcrt基因第76位密码子的单点突变是氯喹耐药性的主要决定因素,但可能不是唯一的决定因素。
The putative key codon (Lys-76 in sensitive parasites and Thr-76 in resistant parasites) of the novel candidate gene for chloroquine resistance, Plasmodium falciparum chloroquine resistance transporter (pfcrt), was determined by polymerase chain reaction-restriction fragment length polymorphism from 111 Cameroonian isolates and was compared with in vivo and in vitro responses to chloroquine. The key codon was significantly associated (P < .001) with responses in vivo (92% sensitivity and 76% specificity) and in vitro (97% sensitivity and 81% specificity). Some discordant results were due to multiclonal infections. The high, but not perfect, correlation between the pfcrt polymorphism and the phenotype implies that a single point mutation in codon 76 of the pfcrt gene is the major, but possibly not the sole, determinant for chloroquine resistance.