Single - nucleotide polymorphisms of artemisinin resistance - related Pfubp1 and Pfap2mu genes in Bioko Island, Equatorial Guinea from 2018 to 2020
10.16250/j.32.1374.2023180
- VernacularTitle:2018—2020年赤道几内亚Bioko岛恶性疟原虫 青蒿素耐药相关基因Pfubp1和Pfap2mu的 单核苷酸多态性分析
- Author:
Taichan ZHANG
1
;
Xueyan LIANG
2
;
Huagui WEI
3
,
4
;
Min LIN
3
,
4
;
Jiangtao CHEN
1
,
5
Author Information
1. Guangdong Medical University, Zhanjiang, Guangdong 524023, China
2. Huizhou Central Hospital Affiliated to Guangdong Medical University, Huizhou, Guangdong 516001, China
3. Chaozhou People’s Hospital Affiliated to Shantou University, Chaozhou, Guangdong 521000, China
4. School of Laboratory Medicine, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, China
5. Huizhou Central Hospital Affiliated to Guangdong Medical University, Huizhou, Guangdong 516001, China
- Publication Type:Journal Article
- Keywords:
Plasmodium falciparum;
Artemisinin - based combination therapy;
Artemisinin;
Drug resistance;
Pfubp1 gene;
Pfap2mu gene;
Single nucleotide polymorphism;
Equatorial Guinea
- From:
Chinese Journal of Schistosomiasis Control
2023;35(6):557-564
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the prevalence of single nucleotide polymorphisms (SNPs) of artemisinin resistance-related Pfubp1 and Pfap2mu genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea, so as to to provide baseline data for the formulation of malaria control strategies in Bioko Island. Methods A total of 184 clinical blood samples were collected from patients with P. falciparum malaria in Bioko Island, Equatorial Guinea from 2018 to 2020, and genomic DNA was extracted. The Pfubp1 and Pfap2mu gene SNPs of P. falciparum were determined using a nested PCR assay and Sanger sequencing, and the gene sequences were aligned. Results There were 159 wild-type P. falciparum isolates (88.83%) from Bioko Island, Equatorial Guinea, and 6 SNPs were identified in 20 Pfubp1-mutant P. falciparum isolates (11.17%), in which 4 non-synonymous mutations were detected, including E1516G, K1520E, D1525E, E1528D. There was only one Pfubp1gene mutation site in 19 Pfubp1-mutant P. falciparum isolates (95.00%), in which non-synonymous mutations accounted for 68.42% (13/19). D1525E and E1528D were identified as major known epidemic mutation sites in the Pfubp1 gene associated with resistance to artemisinin-based combination therapies (ACTs). At amino acid position 1525, there were 178 wild-type P. falciparum isolates (99.44%) and 1 mutant isolate (0.56%), with such a mutation site identified in blood samples in 2018, and at amino acid position 1528, there were 167 wild-type P. falciparum isolates (93.30%) and 12 mutant isolates (6.70%). The proportions of wild-type P. falciparum isolates were 95.72% (134/140), 79.25% (126/159) and 95.83% (161/168) in the target amplification fragments of the three regions in the Pfap2mu gene (Pfap2mu-inner1, Pfap2mu-inner2, Pfap2mu-inner3), respectively. There were 16 different SNPs identified in all successfully sequenced P. falciparum isolates, in which 7 non-synonymous mutations were detected, including S160N, K199T, A475V, S508G, I511M, L595F, and Y603H. There were 7 out of 43 Pfap2mu-mutant P. falciparum isolates (16.28%) that harbored only one gene mutation site, in which non-synonymous mutations accounted for 28.57% (2/7). For the known delayed clearance locus S160N associated with ACTs, there were 143 wild-type (89.94%) and 16 Pfap2mu-mutant P. falciparum isolates (10.06%). Conclusions Both Pfubp1 and Pfap2mu gene mutations were detected in P. falciparum isolates from Bioko Island, Equatorial Guinea from 2018 to 2020, with a low prevalence rate of Pfubp1 gene mutation and a high prevalence rate of Pfap2mu gene mutation. In addition, new mutation sites were identified in the Pfubp1 (E1504E and K1520E) and Pfap2mu genes (A475V and S508G).
