对中国-缅甸边境地区恶性疟原虫分离株抗疟药物敏感性相关遗传标记进行全基因组扫描。

Genome-wide scanning for genetic markers associated with anti-malarial drugs sensitivity of Plasmodium falciparum isolates from the China-Myanmar border region.

作者信息

Tian Yini, Ye Run, Huang Yufu, Zhang Dongmei

机构信息

Department of Tropical Diseases, Faculty of Naval Medicine, Naval Medical University, No.8 Panshan Road, Shanghai, 200433, China.

出版信息

Malar J. 2025 Mar 12;24(1):78. doi: 10.1186/s12936-025-05319-4.

DOI:10.1186/s12936-025-05319-4

PMID:40075412

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11899373/

Abstract

BACKGROUND

Understanding the emergence and spread of anti-malarial resistance, particularly to artemisinin and its partner drugs, is essential for eradicating malaria in worldwide. To identify genetic markers associated with susceptibility to common anti-malarial drugs, the in vitro sensitivities of anti-malarial drugs were evaluated, and a genome-wide association study of Plasmodium falciparum susceptibility in vitro to multiple anti-malarial drugs was conducted.

METHODS

Genomic DNA from 34 samples of P. falciparum collected between 2007 and 2010 in the Nabang-Lazan Valley along the China-Myanmar border was extracted and subjected to whole-genome sequencing. The standard SYBR Green I-based fluorescence assay and RSA assay were used to evaluated the in vitro sensitivities of anti-malarial drugs. Plink v1.90 was used to investigate the associations of genome-wide SNP with in vitro sensitivities to anti-malarial drugs.

RESULTS

The proportion of isolates showed reduced-susceptible to CQ,SP,QN,PPQ and PND were 88.24%,92.59%,8.82%,8.82%,5.88%, respectively. 93.54% of isolates showed high level of the IC values of CQ have a pfcrt CIETS mutations. The isolates with pfdhfr IRNI, NRNL and IRNL mutations showed high SP IC values. SNPs on pfhsp90 and pfevp1 showed significant association with IC values of CQ. Of particular interest is the significant association found between a locus on chromosome 13 and the sensitivity to dihydroartemisinin. This locus is situated within the gene encoding the inner membrane complex protein 1F (IMC1F),which has been found to be associated with the kelch13 compartment in schizont stages of P. falciparum.

CONCLUSIONS

Multiple genetic markers correlating with anti-malarial drug susceptibility were identified in the study, which provide a reference for further investigations into the association between oxidative stress-mediated activity and anti-malarial drugs susceptibility.

摘要

背景

了解抗疟药物耐药性的出现和传播，尤其是对青蒿素及其联合用药的耐药性，对于在全球范围内根除疟疾至关重要。为了确定与常见抗疟药物敏感性相关的遗传标记，评估了抗疟药物的体外敏感性，并对恶性疟原虫对多种抗疟药物的体外敏感性进行了全基因组关联研究。

方法

提取2007年至2010年间在中国-缅甸边境的那邦-拉咱山谷采集的34份恶性疟原虫样本的基因组DNA，并进行全基因组测序。使用基于SYBR Green I的标准荧光测定法和RSA测定法评估抗疟药物的体外敏感性。使用Plink v1.90研究全基因组单核苷酸多态性（SNP）与抗疟药物体外敏感性的关联。

结果

对氯喹（CQ）、磺胺多辛-乙胺嘧啶（SP）、奎宁（QN）、哌喹（PPQ）和咯萘啶（PND）敏感性降低的分离株比例分别为88.24%、92.59%、8.82%、8.82%、5.88%。93.54%对CQ的IC值水平较高的分离株具有pfcrt CIETS突变。具有pfdhfr IRNI、NRNL和IRNL突变的分离株显示出较高的SP IC值。pfhsp90和pfevp1上的SNP与CQ的IC值显示出显著关联。特别值得关注的是，在13号染色体上的一个位点与双氢青蒿素敏感性之间发现了显著关联。该位点位于编码内膜复合蛋白1F（IMC1F）的基因内，已发现其与恶性疟原虫裂殖体阶段的kelch13区室相关。