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MyD88 衔接子样(MAL)基因多态性 rs8177374 与疟原虫(Pf 和 Pv)感染后不同疟疾表现的细胞因子(IFN-γ、TNF-α、IL-10、TGF-β)水平的关系。

Role of MyD88-Adaptor-Like (MAL) Gene Polymorphism rs8177374 and Cytokine (IFN-γ, TNF-α, IL-10, TGF-β) Levels in Diverse Malaria Manifestations upon P. falciparum and P. vivax Infections.

机构信息

Department of Zoology, University of Sargodha, Pakistan.

University of Education, Pakistan.

出版信息

Jpn J Infect Dis. 2023 Nov 22;76(6):358-364. doi: 10.7883/yoken.JJID.2023.079. Epub 2023 Aug 31.

DOI:10.7883/yoken.JJID.2023.079
PMID:37648490
Abstract

This study investigated the role of genetic variant rs8177374 in MAL/TIRAP gene in mediating the cytokine levels of IFN-γ, TNF-α, IL-10, and TGF-β in malaria patients due to Plasmodium falciparum or P. vivax infection. The study included human blood samples collected from patients with malaria (n = 228) and healthy controls (n = 226). P. falciparum and P. vivax groups were established based on the causative species of Plasmodium. Malaria samples were divided into mild and severe malaria groups based on the symptoms that appeared in the patients, according to the WHO criteria. In a previous study, we genotyped rs8177374 via allele specific PCR strategy. In this study, cytokine levels were estimated in the blood plasma of rs8177374 genotype samples via Sandwich Enzyme Linked Immunosorbent Assay kits. Increased IFN-γ and TNF-α levels in presence of CC genotype indicates the role of CC genotype in both severe and mild malaria groups. Enhanced IL-10 levels in the CT genotype and mild malaria groups suggest a role of CT genotype and IL-10 in the mild clinical outcomes of malaria. The rs8177374 polymorphism in MAL/TIRAP plays an important role in malaria pathogenesis.

摘要

这项研究调查了 MAL/TIRAP 基因中遗传变异 rs8177374 在介导疟原虫感染导致的间日疟原虫或恶性疟原虫患者的 IFN-γ、TNF-α、IL-10 和 TGF-β 细胞因子水平中的作用。该研究纳入了来自疟疾病例(n=228)和健康对照者(n=226)的人类血液样本。根据疟原虫的致病物种,将疟疾病例分为间日疟原虫和恶性疟原虫组。根据世界卫生组织(WHO)的标准,根据患者出现的症状,将疟疾病例分为轻度和重度疟疾组。在之前的研究中,我们通过等位基因特异性 PCR 策略对 rs8177374 进行了基因分型。在这项研究中,通过夹心酶联免疫吸附测定试剂盒来估计 rs8177374 基因型样本的血浆细胞因子水平。CC 基因型存在时 IFN-γ 和 TNF-α 水平升高,表明 CC 基因型在重度和轻度疟疾组中都发挥作用。CT 基因型和轻度疟疾组中 IL-10 水平升高,提示 CT 基因型和 IL-10 在疟疾的轻度临床结局中发挥作用。MAL/TIRAP 中的 rs8177374 多态性在疟疾发病机制中起着重要作用。

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