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首页> 外文会议>International Congress of Parasitology >Polymorphisms of Pvmdr1 gene associated with Chloroquine Resistance Phenotype among Plasmodium vivax isolates in Indonesia
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Polymorphisms of Pvmdr1 gene associated with Chloroquine Resistance Phenotype among Plasmodium vivax isolates in Indonesia

机译：与印度尼西亚疟原虫分离株中氯喹耐药表型相关PVMDR1基因的多态性

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Chloroquine (CQ)-resistant Plasmodium vivax, first recorded in 1989, is now known to be a severe problem in much of eastern Indonesia, with more than half of infections exhibiting therapeutic failure. In attempts to identify the genetic mutations linked to resistance to CQ, we analysed P. vivax DNA isolated from 18 subjects classified as having CQ-resistant and 20 subjects classified as having CQ-sensitive vivax malaria following a rigorous phenotyping scheme based upon an in vivo 28-day test. Analysis of the pvcrt-o gene, orthologue of the pfcrt associated with CQ resistance in Plasmodium falciparum, showed no nucletide polymorphisms at sites corresponding to mutations identified as determinants of resistance to CQ in P. falciparum. Analysis of the pvmdr1 gene, orthologue of the pfdmr1 gene that associated with modulation of sensitivity to various antimalarials, including CQ, revealed 2 single nucleotide polymorphisms (SNPs) significantly associated with the CQ-resistant phenotype: 958T (OR = 19; 95% CI = 2.07-173.72) and 976F (OR = 21.25; 95% CI = 5.87 - 78.86 null hypothesis). These statistically significant findings based upon relatively few samples demand expanded work to verify any cause-and-effect relationship between these mutations and the CQ-resistant phenotype in vivax malaria.
机译：氯喹（CQ）-Resistant疟原虫Vivax，于1989年首次记录，现在已知在印度尼西亚东部大部分内部的严重问题，超过一半的感染表现出治疗失败。试图鉴定与抗CQ的抗性有关的遗传突变，我们分析了从分类为具有CQ抗性的18个受试者的P.Vivax DNA分离为具有CQ抗性的20个受试者，该受试者在基于体内的严格表型方向化方案后归类为具有CQ敏感的vivax疟疾。 28天测试。 PVCRT-O基因的分析，与CQ抗性疟原虫中CQ抗性相关的PFCRT的原子学，在对应于鉴定为CQ的抗性抗性的抗性的突变中没有核酸多态性。所述pvmdr1基因的分析，即与各种抗疟药，包括CQ灵敏度的调制相关联的pfdmr1基因的直向同源物，揭示了与耐CQ-表型显著相关联2个单核苷酸多态性（SNP）：958T（OR = 19; 95％CI = 2.07-173.72）和976F（或= 21.25; 95％CI = 5.87 - 78.86零假设）。基于相对较少的样本统计，这些研究结果显著扩大需求工作，以验证这些突变和间日疟耐CQ-表型之间的任何原因和结果的关系。

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