云南省输入性间日疟原虫多药抗性蛋白1基因突变多态性分析

doi:10.12140/j.issn.1000-7423.2023.04.002

中国寄生虫学与寄生虫病杂志 ›› 2023, Vol. 41 ›› Issue (4): 404-411.doi: 10.12140/j.issn.1000-7423.2023.04.002

云南省输入性间日疟原虫多药抗性蛋白1基因突变多态性分析

丁红芸¹(), 董莹²^,^*(), 徐艳春², 邓艳², 刘言², 吴静², 陈梦妮², 张苍林²

1 昆明理工大学生命科学与技术学院，云南昆明 650500
2 云南省寄生虫病防治所，云南省疟疾研究中心，云南省虫媒传染病防控研究重点实验室，普洱 665000

收稿日期:2022-10-13 修回日期:2023-01-27 出版日期:2023-08-30 发布日期:2023-09-06
通讯作者: *董莹（1964-），女，本科，主任医师，从事疟疾病原学及分子生物学研究。E-mail：luxidongying@126.com
作者简介:丁红芸（1998-），女，硕士研究生，从事疟疾的分子流行病学研究。E-mail：1053343328@qq.com
基金资助:
国家自然科学基金(81660559);国家自然科学基金(82160637)

Polymorphism analysis of multidrug resistance protein 1 gene in imported Plasmodium vivax in Yunnan Province

DING Hongyun¹(), DONG Ying²^,^*(), XU Yanchun², DENG Yan², LIU Yan², WU Jing², CHEN Mengni², ZHANG Canglin²

1 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, China
2 Yunnan Institute of Parasitic Diseases, Yunnan Center of Malaria Research, Yunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Puer 665000, China

Received:2022-10-13 Revised:2023-01-27 Online:2023-08-30 Published:2023-09-06
Contact: *E-mail: luxidongying@126.com
Supported by:
National Natural Science Foundation of China(81660559);National Natural Science Foundation of China(82160637)

摘要/Abstract

摘要：

目的分析云南省输入性间日疟原虫的多药抗性蛋白1基因（Pvmdr1）突变多态性。方法对云南省2020年和2021年诊断为间日疟原虫感染的病例血样进行Pvmdr1全基因扩增及测序，以间日疟原虫Sal-Ⅰ分离株的序列（GenBank登录号：NC_009915.1）为模板设计PCR反应引物，用MEGA 5.04软件与编码区参比序列（GenBank登录号：XM_001613678.1）进行比对，用DnaSP 6.11.01软件分析单倍型和单核苷酸多态（SNP）位点及其突变类型，并计算核酸多样性指数π、单倍型期望杂合度（He）等，用Network 10.0软件构建中介网络进化图。结果共收集276份输入性间日疟患者血样，其中自缅甸感染病例占99.3%（274/276），自非洲、巴基斯坦感染各占0.4%（1/276）。259份血样扩增获得4 392 bp的Pvmdr1全基因序列，提交GenBank获得的登录号为OP559204~OP559462。259条DNA序列π、Ka/Ks比值分别为0.000 76和3.600 6，共检出22个SNP，包括13个非同义突变和9个同义突变。仅c.4074C>T位点突变在2020、2021年的检出率[15.0%（21/140）、5.9%（7/119）]差异有统计学意义（χ² = 5.546，P < 0.05）。次等位位点为c.1587A>G（97.9%，253/259），新检出SNP包括c.2499G>T（2.3%，6/259）、c.3358C>T（0.4%，1/259）、c.3832C>T（0.4%，1/259）。c.3064C>T、c.4065A>G、c.3358C>T和c.3832C>T突变位点仅在2021年的患者血样中检出，其中前2个SNP从非洲感染的分离株中检出，后2个SNP从缅甸感染的分离株中检出。259条Pvmdr1完整编码区与参比序列（单倍型Hap_1）比对，识别出26种单倍型（Hap_2~Hap_27），均为参比序列（单倍型Hap_1）的突变型，He为0.890 7。其中，Hap_8的检出率最高（18.5%，48/259），非洲感染分离株中仅检出Hap_19。2020、2021年的患者血样中检出的单倍型种类分别有15和22种，当年独有的单倍型分别为4和10种。Hap_10在2020、2021年患者血样中的检出率分别为15.0%（21/140）和3.4%（4/119），差异有统计学意义（χ² = 22.264，P < 0.05）。不同单倍型的多重突变识别结果显示，4重、5重、6重、7重、9重、10重突变在26种单倍型中的占比分别为0.4%（1/26）、19.2%（5/26）、38.5%（10/26）、30.8%（8/26）、0.4%（1/26）、0.4%（1/26）。中介网络图显示，26种单倍型以单倍型Hap_1为起始，经4重突变（Hap_24），向5重、6重、7重、9重和10重突变逐级进化并远离起始点。结论云南省输入性间日原虫Pvmdr1基因突变存在高度多态性。

关键词: 间日疟原虫, 多药抗性蛋白1, 突变, 云南省

Abstract:

Objective To analyze the polymorphism of Plasmodium vivax multidrug resistance protein 1 gene (Pvmdr1) from imported vivax malaria patients in Yunnan Province. Methods The whole Pvmdr1 gene was amplified and sequenced in the blood samples of patients who diagnosed with vivax malaria in 2020 and 2021 in Yunnan Province. The sequence of P. vivax SalⅠ isolate (GenBank accession number: NC_009915.1) was taken as the reference sequence for designing primers. MEGA 5.04 software was used to align the spliced sequences with the coding region reference sequence (GenBank accession number: XM_001613678.1). Haplotype and single nucleotide polymorphism (SNP) sites and their mutation types, nucleotide diversity π, expected heterozygosity (He), etc were analyzed by DnaSP 6.11.01. Haplotype medium network diagram was constructed using Network 10.0 Software. Results A total of 276 blood samples were collected from vivax malaria patients and were imported from overseas. The full gene sequences with 4 392 bp of Pvmdr1 were obtained from 259 blood samples, and the accession numbers were OP559204-OP559462 assigned by GenBank. The π of 259 DNA coding sequences was 0.000 76. A total of 22 SNPs were detected from 259 coding sequences, including 13 non-synonymous mutant and 9 synonymous mutant loci. Only the detection rate difference of c.4074C>T mutation between 2020 and 2021 [15.0% (21/140), 5.9% (7/119)] was statistically significant (χ² = 5.546, P < 0.05). The minor allele frequency was c.1587A>G (97.9%, 253/259), and the newly discovered SNPs included c.2499G>T (2.3%, 6/259), c.3358C>T (0.4%, 1/259), and c.3832C>T (0.4%, 1/259). All of c.3064C>T, c.4065A>G, c.3358C>T and c.3832C>T mutant sites were detected from the blood samples in 2021. The 259 complete coding region sequences of Pvmdr1 were defined as 26 haplotypes (Hap_2-Hap_27) by comparison with the reference sequence (haplotype Hap_1, all of which were mutant type haplotypes, and He was 0.890 7. Among them, the detection rate of Hap_8 was the highest (18.5%, 48/259). There were 15 and 22 haplotypes found from blood samples in 2020 and 2021, respectively. Among them, 4 haplotypes were only detected in blood samples from 2020, and 10 haplotype were only detected in blood samples from 2021. The difference of Hap_10 detection rate between 2020 and 2021 [15.0% (21/140), 3.4% (4/119)] was statistically significant (χ² = 22.264, P < 0.05). The proportions of quadruple, quintuple, six-fold, seven-fold, nine-fold and ten-fold multiple mutations in 26 haplotypes were 0.4% (1/26), 19.2% (5/26), 38.5% (10/26), 30.8% (8/26), 0.4% (1/26), and 0.4% (1/26), respectively. The haplotype medium network diagram displayed that the gradual evolution of 26 haplotypes started with Hap_1, and then passed through quadruple mutation (Hap_24), moved towards quintuple, six-fold, seven-fold, nine-fold, and ten-fold multiple mutations away from. Conclusion There is high polymorphism in the Pvmdr1 gene in the P. vivax from the imported vivax malaria cases in Yunnan Province.

Key words: Plasmodium vivax, Multidrug resistance protein 1, Mutation, Yunnan Province

中图分类号:

R382.311

丁红芸, 董莹, 徐艳春, 邓艳, 刘言, 吴静, 陈梦妮, 张苍林. 云南省输入性间日疟原虫多药抗性蛋白1基因突变多态性分析[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(4): 404-411.

DING Hongyun, DONG Ying, XU Yanchun, DENG Yan, LIU Yan, WU Jing, CHEN Mengni, ZHANG Canglin. Polymorphism analysis of multidrug resistance protein 1 gene in imported Plasmodium vivax in Yunnan Province[J]. Chinese Journal of Parasitology and Parasitic Diseases, 2023, 41(4): 404-411.

图/表 5

表1

图1

表2

表3

云南省输入性间日疟原虫Pvmdr1基因的不同突变单倍型

序号 Order	单倍型 Haplotype	不同程度的多重突变型 Multiple mutants of different degrees		单倍型数（检出率/%） No. haplotype (Detection rate/%)
序号 Order	单倍型 Haplotype	类型 Type	重性 Multiplicity	2020 （n = 140）	2021 （n = 119）	合计 Total
1	Hap_24	G698S/M908L/T958M/F1076L	4	1(0.7)	-	1(0.4)
2	Hap_8	T529T/G698S/M908L/T958M/F1076L	5	29(20.7)	19(16.0)	48(18.5)
3	Hap_9	T529T/M908L/T958M/F1076L/K1393N	5	-	4(3.4)	4(1.5)
4	Hap_21	G698S/L845F/M908L/T958M/F1076L	5	2(1.4)	1(0.8)	3(1.2)
5	Hap_26	K44K/G698S/M908L/T958M/F1076L	5	1(0.7)	-	1(0.4)
6	Hap_27	K44K/T529T/M908L/T958M/F1076L	5	1(0.7)	-	1(0.4)
7	Hap_7	S513R/T529T/G698S/M908L/T958M/K1393N	6	6(4.3)	4(3.4)	10(3.9)
8	Hap_4	P8L/L310L/T529T/M908L/T958M/F1076L	6	19(13.6)	24(20.2)	43(16.6)
9	Hap_10	S513R/T529T/G698S/M908L/T958M/S1358S	6	21(15.0)	4(3.4)^a	25(9.7)
10	Hap_12	T529T/G698S/M908L/T958M/F1076L/K1393N	6	-	1(0.8)	1(0.4)
11	Hap_13	S513R/T529T/G698S/M908L/T958M/F1076L	6	-	1(0.8)	1(0.4)
12	Hap_16	S513R/T529T/M908L/T958M/F1076L/S1358S	6	-	1(0.8)	1(0.4)
13	Hap_18	T529T/G698S/M908L/T958M/F1076L/S1358S	6	-	1(0.8)	1(0.4)
14	Hap_20	T409M/T529T/M908L/T958M/F1076L/K1393N	6	-	1(0.8)	1(0.4)
15	Hap_23	K44K/T529T/G698S/M908L/T958M/F1076L	6	-	1(0.8)	1(0.4)
16	Hap_25	T529T/G698S/A861E/M908L/T958M/F1076L	6	1(0.7)	-	1(0.4)
17	Hap_2	K44K/T529T/G698S/L845F/M908L/T958M/F1076L	7	10(7.1)	14(11.8)	24(9.3)
18	Hap_3	P8L/L310L/T529T/G698S/M908L/T958M/F1076L	7	-	1(0.8)	1(0.4)
19	Hap_5	K44K/T529T/G698S/A861E/M908L/T958M/F1076L	7	15(10.7)	17(14.3)	32(12.4)
20	Hap_6	K44K/T529T/G698S/M908L/T958M/F1076L/S1450L	7	16(11.4)	13(11.0)	29(11.2)
21	Hap_11	K44K/T529T/G698S/M833I/M908L/T958M/F1076L	7	3(2.1)	3(2.5)	6(2.3)
22	Hap_14	T409M/T529T/G698S/M908L/T958M/F1076L/K1393N	7	8(5.7)	4(3.4)	12(4.6)
23	Hap_17	K44K/S513R/T529T/G698S/M908L/T958M/S1358S	7	-	1(0.8)	1(0.4)
24	Hap_19	S513R/T529T/M908L/T958M/L1022L/F1076L/K1355K	7	-	1(0.8)	1(0.4)
25	Hap_22	K44K/G698S/L845F/M908L/T958M/F1076L/L1120L/L1278L/S1450L	9	-	1(0.8)	1(0.4)
26	Hap_15	K44K/G520D/T529T/G698S/A861E/M908L/T958M/F1076L/I1348I/S1450L	10	7(5.0)	2(1.7)	9(3.5)

表3

图2

参考文献 37

[1]	Xia ZG, Feng J, Zhang L, et al. Achieving malaria elimination in China: analysis on implementation and effectiveness of the surveillance-response system[J]. Chin J Parasitol Parasit Dis, 2021, 39(6): 733-741. (in Chinese)
	(夏志贵, 丰俊, 张丽, 等. 中国消除疟疾: 监测响应系统的实施与成效分析[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(6): 733-741.)
[2]	Zhang L, Feng J, Zhang SS, et al. Epidemiological characteristics of malaria in China, 2016[J]. Chin J Parasitol Parasit Dis, 2017, 35(6): 515-519. (in Chinese)
	(张丽, 丰俊, 张少森, 等. 2016年全国疟疾疫情特征分析[J]. 中国寄生虫学与寄生虫病杂志, 2017, 35(6): 515-519.)
[3]	Zhang L, Yi BY, Xia ZG, et al. Epidemiological characteristics of malaria in China, 2021[J]. Chin J Parasitol Parasit Dis, 2022, 40(2): 135-139. (in Chinese)
	(张丽, 易博禹, 夏志贵, 等. 2021年全国疟疾疫情特征分析[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(2): 135-139.)
[4]	Rieckmann KH, Davis DR, Hutton DC. Plasmodium vivax resistance to chloroquine?[J]. Lancet, 1989, 334(8673): 1183-1184. doi: 10.1016/S0140-6736(89)91792-3
[5]	(Myat-Phone-Kyaw, Myint-Oo, Myint-Lwin, et al. Emergence of chloroquine-resistant Plasmodium vivax in Myanmar (Burma)[J]. Trans R Soc Trop Med Hyg, 1993, 87(6): 687. doi: 10.1016/0035-9203(93)90294-Z
[6]	Singh RK. Emergence of chloroquine-resistant vivax malaria in South Bihar (India)[J]. Trans R Soc Trop Med Hyg, 2000, 94(3): 327. doi: 10.1016/S0035-9203(00)90344-4
[7]	Phan GT, de Vries PJ, Tran BQ, et al. Artemisinin or chloroquine for blood stage Plasmodium vivax malaria in Vietnam[J]. Trop Med Int Health, 2002, 7(10): 858-864. doi: 10.1046/j.1365-3156.2002.00948.x
[8]	Musset L, Heugas C, Naldjinan R, et al. Emergence of Plasmodium vivax resistance to chloroquine in French Guiana[J]. Antimicrob Agents Chemother, 2019, 63(11): e02116-e02118.
[9]	Picot S, Brega S, Gérôme P, et al. Absence of nucleotide polymorphism in a Plasmodium vivax multidrug resistance gene after failure of mefloquine prophylaxis in French Guyana[J]. Trans R Soc Trop Med Hyg, 2005, 99(3): 234-237. doi: 10.1016/j.trstmh.2004.09.007
[10]	Marfurt J, de Monbrison F, Brega S, et al. Molecular markers of in vivo Plasmodium vivax resistance to amodiaquine plus sulfadoxine-pyrimethamine: mutations in Pvdhfr and Pvmdr1[J]. J Infect Dis, 2008, 198(3): 409-417. doi: 10.1086/589882 pmid: 18582193
[11]	Zeng WL, Zhao H, Zhao W, et al. Molecular surveillance and Ex vivo drug susceptibilities of Plasmodium vivax isolates from the China-Myanmar border[J]. Front Cell Infect Microbiol, 2021, 11: 738075. doi: 10.3389/fcimb.2021.738075
[12]	Li JY, Zhang J, Li Q, et al. Ex vivo susceptibilities of Plasmodium vivax isolates from the China-Myanmar border to antimalarial drugs and association with polymorphisms in Pvmdr1 and Pvcrt-o genes[J]. PLoS Negl Trop Dis, 2020, 14(6): e0008255. doi: 10.1371/journal.pntd.0008255
[13]	Xu SL, Zeng WL, Ngassa Mbenda HG, et al. Efficacy of directly-observed chloroquine-primaquine treatment for uncomplicated acute Plasmodium vivax malaria in northeast Myanmar: a prospective open-label efficacy trial[J]. Travel Med Infect Dis, 2020, 36: 101499. doi: 10.1016/j.tmaid.2019.101499
[14]	Ratcliff A, Siswantoro H, Kenangalem E, et al. Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine-pyrimethamine in southern Papua, Indonesia[J]. Trans R Soc Trop Med Hyg, 2007, 101(4): 351-359. doi: 10.1016/j.trstmh.2006.06.008
[15]	Ganguly S, Saha P, Guha SK, et al. In vivo therapeutic efficacy of chloroquine alone or in combination with primaquine against vivax malaria in Kolkata, West Bengal, India, and polymorphism in Pvmdr1 and Pvcrt-o genes[J]. Antimicrob Agents Chemother, 2013, 57(3): 1246-1251. doi: 10.1128/AAC.02050-12
[16]	Pukrittayakamee S, Imwong M, Looareesuwan S, et al. Therapeutic responses to antimalarial and antibacterial drugs in vivax malaria[J]. Acta Trop, 2004, 89(3): 351-356. pmid: 14744561
[17]	Wang ZS, Wei CY, Pan YC, et al. Polymorphisms of potential drug resistant molecular markers in Plasmodium vivax from China-Myanmar border during 2008—2017[J]. Infect Dis Poverty, 2022, 11: 43. doi: 10.1186/s40249-022-00964-2
[18]	WHO. Malaria surveillance, monitoring & evaluation: a reference manua[M]. Geneva: WHO, 2018: 69-81.
[19]	Chung DI, Jeong S, Dinzouna-Boutamba SD, et al. Evaluation of single nucleotide polymorphisms of Pvmdr1 and microsatellite genotype in Plasmodium vivax isolates from Republic of Korea military personnel[J]. Malar J, 2015, 14: 336. doi: 10.1186/s12936-015-0845-6
[20]	Nomura T, Carlton JM, Baird JK, et al. Evidence for different mechanisms of chloroquine resistance in 2 Plasmodium species that cause human malaria[J]. J Infect Dis, 2001, 183(11): 1653-1661. pmid: 11343215
[21]	Sá JM, Nomura T, Neves JD, et al. Plasmodium vivax: allele variants of the mdr1 gene do not associate with chloroquine resistance among isolates from Brazil, Papua, and monkey-adapted strains[J]. Exp Parasitol, 2005, 109(4): 256-259. doi: 10.1016/j.exppara.2004.12.005
[22]	Carlton J. The Plasmodium vivax genome sequencing project[J]. Trends Parasitol, 2003, 19(5): 227-231. pmid: 12763429
[23]	Walliker D, Quakyi IA, Wellems TE, et al. Genetic analysis of the human malaria parasite Plasmodium falciparum[J]. Science, 1987, 236(4809): 1661-1666. pmid: 3299700
[24]	McConkey GA, Waters AP, McCutchan TF. The generation of genetic diversity in malaria parasites[J]. Annu Rev Microbiol, 1990, 44: 479-498. pmid: 2252391
[25]	Ngassa Mbenda HG, Wang ML, Guo J, et al. Evolution of the Plasmodium vivax multidrug resistance 1 gene in the Greater Mekong Subregion during malaria elimination[J]. Parasit Vectors, 2020, 13(1): 67. doi: 10.1186/s13071-020-3934-5
[26]	Kittichai V, Nguitragool W, Ngassa Mbenda HG, et al. Genetic diversity of the Plasmodium vivax multidrug resistance 1 gene in Thai parasite populations[J]. Infect Genet Evol, 2018, 64: 168-177. doi: 10.1016/j.meegid.2018.06.027
[27]	Villena FE, Maguiña JL, Santolalla ML, et al. Molecular surveillance of the Plasmodium vivax multidrug resistance 1 gene in Peru between 2006 and 2015[J]. Malar J, 2020, 19(1): 450. doi: 10.1186/s12936-020-03519-8
[28]	Cubides JR, Camargo-Ayala PA, Niño CH, et al. Simultaneous detection of Plasmodium vivax dhfr, dhps, mdr1 and crt-o resistance-associated mutations in the Colombian Amazonian region[J]. Malar J, 2018, 17(1): 130. doi: 10.1186/s12936-018-2286-5
[29]	Huang F, Li SG, Tian P, et al. Genetic polymorphisms in genes associated with drug resistance in Plasmodium vivax parasites from northeastern Myanmar[J]. Malar J, 2022, 21(1): 66. doi: 10.1186/s12936-022-04084-y
[30]	Orjuela-Sánchez P, de Santana Filho FS, Machado-Lima A, et al. Analysis of single-nucleotide polymorphisms in the crt-o and mdr1 genes of Plasmodium vivax among chloroquine-resistant isolates from the Brazilian Amazon region[J]. Antimicrob Agents Chemother, 2009, 53(8): 3561-3564. doi: 10.1128/AAC.00004-09 pmid: 19451296
[31]	Tacoli C, Gai PP, Siegert K, et al. Characterization of Plasmodium vivax Pvmdr1 polymorphisms in isolates from mangaluru, India[J]. Am J Trop Med Hyg, 2019, 101(2): 416-417. doi: 10.4269/ajtmh.19-0224
[32]	Diez Benavente E, Ward Z, Chan W, et al. Genomic variation in Plasmodium vivax malaria reveals regions under selective pressure[J]. PLoS One, 2017, 12(5): e0177134. doi: 10.1371/journal.pone.0177134
[33]	Imwong M, Pukrittayakamee S, Pongtavornpinyo W, et al. Gene amplification of the multidrug resistance 1 gene of Plasmodium vivax isolates from Thailand, Laos, and Myanmar[J]. Antimicrob Agents Chemother, 2008, 52(7): 2657-2659. doi: 10.1128/AAC.01459-07
[34]	González-Cerón L, Montoya A, Corzo-Gómez JC, et al. Genetic diversity and natural selection of Plasmodium vivax multi-drug resistant gene (Pvmdr1) in Mesoamerica[J]. Malar J, 2017, 16(1): 261. doi: 10.1186/s12936-017-1905-x
[35]	Zhao Y, Wang L, Soe MT, et al. Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China-Myanmar border[J]. Malar J, 2020, 19(1): 281. doi: 10.1186/s12936-020-03354-x
[36]	Lu F, Lim CS, Nam DH, et al. Genetic polymorphism in Pvmdr1 and Pvcrt-o genes in relation to in vitro drug susceptibility of Plasmodium vivax isolates from malaria-endemic countries[J]. Acta Trop, 2011, 117(2): 69-75. doi: 10.1016/j.actatropica.2010.08.011
[37]	Barnadas C, Ratsimbasoa A, Tichit M, et al. Plasmodium vivax resistance to chloroquine in Madagascar: clinical efficacy and polymorphisms in Pvmdr1 and Pvcrt-o genes[J]. Antimicrob Agents Chemother, 2008, 52(12): 4233-4240. doi: 10.1128/AAC.00578-08 pmid: 18809933

片段 Fragment	引物名称 Primer name	引物序列（5'→3'） Primer sequence (5'→3')	PCR轮次 PCR round	产物长度/bp Product length/bp
F1	MD-1F	TAACTCCTCACCGTTTGGGAAT	第一轮	1 245
F1	MD-1R	TCATTGTTTGGTTGCTGGTTGC	First round	1 245
F2	MD-2F	TTTATTACCATATTTACGTACGCAAG	第一轮	1 385
F2	MD-2R	ATGATGATCGTAATTCTGTTTTCG	First round	1 385
F3	MD-3F1	CAACATCAAGTATAGTTTGTACAGC	第一轮	1 368
	MD-3R1	TGAACATCTCTGTTAATATGTGCTG	First round	1 368
	MD-3F2	TTAGTGTTTCGAAGAAGGTGCA	第二轮	959
	MD-3R2	GTAGAGGGAGTACTTATTCGAGT	Second round	959
F4	MD-4F	GCAGCATTTATAAGGACTCCG	第一轮	1 387
F4	MD-4R	CTCATCACGGTAGATTTGCC	First round	1 387
F5	MD-5F1	GAGAAGGCTATTGATTATTCGAAT	第一轮	1 571
	MD-5R1	TTAACTATGTTTACTACGGTTAAGGG	First round
	MD-5F2	TCCTTCGAAAGGTACTACCCACT	第二轮
	MD-5R2	CATATGATCTGTGCACGTGCAT	Second round

云南省输入性间日疟原虫多药抗性蛋白1基因突变多态性分析

Polymorphism analysis of multidrug resistance protein 1 gene in imported Plasmodium vivax in Yunnan Province

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 5

参考文献 37

相关文章 15

编辑推荐

Metrics

本文评价

[1]	李奔福, 王正青, 徐倩, 字金荣, 严信留, 彭佳, 李建雄, 蔡璇, 吴方伟, 杨亚明. 云南省细粒棘球绦虫线粒体co1和nd1基因序列分析[J]. 中国寄生虫学与寄生虫病杂志, 2023, 41(3): 306-311.
[2]	王冠熙, 李雅姝, 李月月, 曹园园, 杨蒙蒙, 张梅花, 吴竞瑶, 梁成, 李菊林, 周华云, 唐建霞, 朱国鼎. 江苏省白纹伊蚊对溴氰菊酯抗性及击倒抗性突变分析[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(4): 468-474.
[3]	石天琪, 陈军虎. 间日疟原虫入侵网织红细胞相关蛋白的研究进展[J]. 中国寄生虫学与寄生虫病杂志, 2022, 40(3): 396-401.
[4]	普丽花, 张兴泽, 关少君, 程文杰, 邹丰才, 毛华明, 杨建发. 云南省奶牛芽囊原虫的感染情况及其基因亚型分析[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(6): 809-815.
[5]	字金荣, 汪丽波, 杨亚明, 李奔福, 严信留, 彭佳, 蔡璇, 王正青, 杜尊伟, 吴方伟. 2015年云南省人群蛔虫感染现状调查[J]. 中国寄生虫学与寄生虫病杂志, 2021, 39(2): 273-277.
[6]	吴方伟, 汪丽波, 李奔福, 严信留, 字金荣, 彭佳, 蔡璇, 保雪莹, 杨亚明. 2015年云南省人体钩虫感染现状调查[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(6): 781-784.
[7]	金行一, 张玲玲, 朱素娟, 徐卫民, 陈珺芳, 阮卫, 姚立农, 陈华良. 间日疟原虫裂殖子表面蛋白1和环子孢子蛋白基因多态性分析[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(3): 323-331.
[8]	刘淑萍, 董莹, 徐艳春, 刘言, 邓艳, 张苍林, 陈梦妮. 云南省间日疟患者G6PD基因编码区的突变分析[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(2): 146-151.
[9]	徐艳春, 董莹, 邓艳, 毛祥华, 陈梦妮, 张苍林, 江陆斌. 云南省不同感染来源间日疟原虫环子孢子蛋白基因多态和种群结构分析[J]. 中国寄生虫学与寄生虫病杂志, 2020, 38(1): 67-73.
[10]	李奔福, 吴方伟, 严信留, 字金荣, 彭佳, 保雪莹, 蔡璇, 王正青, 杨亚明. 云南省藏东-川西生态区人体重点寄生虫病流行现状调查[J]. 中国寄生虫学与寄生虫病杂志, 2019, 37(6): 718-722.
[11]	田春艳, 陈蓓, 卢帅, 文丽梅, 赵军, 郑璇, 库尔班泥沙·阿马洪, 高旖, 王建华. 阿霉素体外抗细粒棘球蚴原头节作用研究[J]. 中国寄生虫学与寄生虫病杂志, 2019, 37(5): 571-576.
[12]	李奔福, 吴方伟, 严信留, 字金荣, 彭佳, 保雪莹, 蔡璇, 杨亚明. 2012-2017年云南省棘球蚴病流行病学分析[J]. 中国寄生虫学与寄生虫病杂志, 2019, 37(5): 576-582.
[13]	董莹, 刘淑萍, 徐艳春, 刘言, 邓艳, 陈梦妮. 云南省1例伯氨喹诱发溶血患者的G6PD基因编码区突变分析及酶蛋白空间结构预测[J]. 中国寄生虫学与寄生虫病杂志, 2019, 37(4): 399-405.
[14]	杨锐, 郑宇婷, 杨晓羽, 董利民, 林祖锐, 周耀武, 曾旭灿, 李鸿斌, 姜进勇. 云南省边境地区景洪市疟疾媒介调查[J]. 中国寄生虫学与寄生虫病杂志, 2019, 37(4): 406-410.
[15]	张苍林, 保雪莹, 彭佳, 字金荣, 冉甄, 卢娜, 杨亚明. 云南省西南地区福寿螺COⅠ基因序列单核苷酸多态性分析[J]. 中国寄生虫学与寄生虫病杂志, 2019, 37(1): 75-81.