磺胺多辛-乙胺嘧啶治疗应答中 基因和 基因高频突变：来自非洲返回中国移民的横断面调查。
High Frequency Mutations in and of in Response to Sulfadoxine-Pyrimethamine: A Cross-Sectional Survey in Returning Chinese Migrants From Africa.
机构信息
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, China.
School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
Front Cell Infect Microbiol. 2021 Sep 8;11:673194. doi: 10.3389/fcimb.2021.673194. eCollection 2021.
BACKGROUND
Sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment in Africa against infection. However, increasing SP resistance (SPR) of affects the therapeutic efficacy of SP, and (encoding dihydrofolate reductase) and (encoding dihydropteroate synthase) genes are widely used as molecular markers for SPR surveillance. In the present study, we analyzed single nucleotide polymorphisms (SNPs) of and in isolated from infected Chinese migrant workers returning from Africa.
METHODS
In total, 159 blood samples from -infected workers who had returned from Africa to Anhui, Shangdong, and Guangxi provinces were successfully detected and analyzed from 2017 to 2019. The SNPs in and were analyzed using nested PCR. The genotypes and linkage disequilibrium (LD) were analyzed using Haploview.
RESULTS
High frequencies of the Asn51Ile (N51I), Cys59Arg(C59R), and Ser108Asn(S108N) mutant alleles were observed, with mutation frequencies of 97.60, 87.43, and 97.01% in , respectively. A triple mutation (IRN) in was the most prevalent haplotype (86.83%). Six point mutations were detected in DNA fragment, Ile431Val (I431V), Ser436Ala (S436A), Ala437Gly (A437G), Lys540Glu(K540E), Ala581Gly(A581G), Ala613Ser(A613S). The K540E (27.67%) was the most predominant allele, followed by S436A (27.04%), and a single mutant haplotype (SGKAA; 62.66%) was predominant in . In total, 5 haplotypes of the gene and 13 haplotypes of the gene were identified. A total of 130 isolates with 12 unique haplotypes were found in the combined haplotypes, most of them (n = 85, 65.38%) carried quadruple allele combinations (CIRNI-SGKAA).
CONCLUSION
A high prevalence of point mutations in the and genes of isolates was detected among Chinese migrant workers returning from Africa. Therefore, continuous molecular monitoring of Sulfadoxine-Pyrimethemine combined therapeutic monitoring of artemisinin combination therapy (ACT) efficacy and additional control efforts among migrant workers are urgently needed.
背景
磺胺多辛-乙胺嘧啶（SP）被推荐用于非洲间歇性预防治疗感染。然而，增加的磺胺多辛耐药性（SPR）影响 SP 的治疗效果，和（编码二氢叶酸还原酶）和（编码二氢蝶酸合酶）基因被广泛用作 SPR 监测的分子标记。在本研究中，我们分析了从返回非洲的感染中国农民工中分离出的的单核苷酸多态性（SNP）。
方法
从 2017 年至 2019 年，共成功检测并分析了来自安徽、山东和广西等省份的 159 名从非洲返回的感染 - 工人的血液样本。使用嵌套 PCR 分析和中的 SNP。使用 Haploview 分析基因型和连锁不平衡（LD）。
结果
观察到高频率的天冬氨酸 51 异亮氨酸（N51I）、半胱氨酸 59 精氨酸（C59R）和丝氨酸 108 天冬酰胺（S108N）突变等位基因，分别为 97.60%、87.43%和 97.01%。三重突变（IRN）是最常见的单倍型（86.83%）。在 DNA 片段中检测到 6 个点突变，异亮氨酸 431 缬氨酸（I431V）、丝氨酸 436 丙氨酸（S436A）、丙氨酸 437 甘氨酸（A437G）、赖氨酸 540 谷氨酸（K540E）、丙氨酸 581 甘氨酸（A581G）、丙氨酸 613 丝氨酸（A613S）。最主要的等位基因是 540 赖氨酸谷氨酸（K540E）（27.67%），其次是 S436A（27.04%），单突变单倍型（SGKAA；62.66%）在中占主导地位。共鉴定出基因的 5 种单倍型和基因的 13 种单倍型。在组合单倍型中发现了 120 株 12 种独特单倍型的分离株，其中大多数（n=85，65.38%）携带四重等位基因组合（CIRNI-SGKAA）。
结论
在中国农民工中，从返回非洲的农民工中分离出的和基因中检测到点突变的高发生率。因此，迫切需要对农民工进行磺胺多辛-乙胺嘧啶联合青蒿素类复方疗法（ACT）疗效的持续分子监测和额外的控制措施。
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