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TOLLIP mRNA表达及TOLLIP rs5743899A/G、TOLLIP rs3750920C/T和IL-10 -1082G/A单核苷酸多态性与结核病易感性的关联

Association of TOLLIP mRNA Expression and TOLLIP rs5743899A/G, TOLLIP rs3750920C/T, and IL-10 -1082G/A Single-Nucleotide Polymorphisms with Susceptibility to Tuberculosis.

作者信息

Nagiyev Togrul, Eker Emel, Uckayabasi Ali, Hanta Ismail, Kayar Begum, Binokay Hulya, Sertdemir Yasar, Koksal Fatih

机构信息

Department of Medical Microbiology, Faculty of Medicine, Cukurova University, Adana, Turkey.

Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Harran University, Sanliurfa, Turkey.

出版信息

Curr Microbiol. 2025 Feb 25;82(4):154. doi: 10.1007/s00284-025-04144-x.

DOI:10.1007/s00284-025-04144-x
PMID:39998652
Abstract

The early innate host immune response is crucial in the susceptibility to tuberculosis (TB). This study aimed to investigate the potential role of Toll-interacting protein (TOLLIP), a negative regulator of the human innate immune response, and interleukin-10 (IL-10), an anti-inflammatory cytokine, in susceptibility to TB. The peripheral blood mononuclear cells of 30 active pulmonary TB patients and 30 healthy volunteers were included. TOLLIP mRNA expression levels, single nucleotide polymorphisms (SNPs) of the TOLLIP gene, such as rs5743899A/G and rs3750920C/T, and IL-10 -1082G/A SNP were detected using real-time PCR, PCR-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system-PCR (ARMS-PCR), respectively. TOLLIP mRNA expression levels were significantly higher in TB patients than in healthy controls (expression fold difference = 2.72, the delta-delta Ct method, also known as the 2-∆∆Ct method). The heterozygous (GA) genotype of the IL-10 -1080G/A polymorphism was significantly predominant among the patient group (p = 0.02, Hardy-Weinberg equilibrium). However, the Kruskal‒Wallis analysis found no significant relationship between TOLLIP mRNA expression levels and SNPs. TOLLIP mRNA and IL-10 -1082G/A SNP were assessed as potential biomarkers to predict TB susceptibility. For more significant results, they should be examined with other negative regulators of innate immunity and other immune factors associated with susceptibility to TB. Our study is the first to investigate the association of TOLLIP polymorphisms and expression levels with TB susceptibility in Turkey.

摘要

早期先天性宿主免疫反应在结核病(TB)易感性中起关键作用。本研究旨在探讨人先天性免疫反应的负调节因子Toll相互作用蛋白(TOLLIP)和抗炎细胞因子白细胞介素-10(IL-10)在结核病易感性中的潜在作用。纳入了30例活动性肺结核患者和30名健康志愿者的外周血单个核细胞。分别采用实时荧光定量PCR、聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和扩增阻滞突变系统-PCR(ARMS-PCR)检测TOLLIP mRNA表达水平、TOLLIP基因的单核苷酸多态性(SNP),如rs5743899A/G和rs3750920C/T,以及IL-10 -1082G/A SNP。肺结核患者的TOLLIP mRNA表达水平显著高于健康对照(表达倍数差异=2.72,ΔΔCt法,也称为2-ΔΔCt法)。IL-10 -1080G/A多态性的杂合子(GA)基因型在患者组中显著占优势(p=0.02,哈迪-温伯格平衡)。然而,Kruskal-Wallis分析发现TOLLIP mRNA表达水平与SNP之间无显著关系。评估TOLLIP mRNA和IL-10 -1082G/A SNP作为预测结核病易感性的潜在生物标志物。为了获得更显著的结果,应与其他先天性免疫负调节因子和其他与结核病易感性相关的免疫因子一起进行检测。我们的研究首次在土耳其调查了TOLLIP多态性和表达水平与结核病易感性的关联。

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本文引用的文献

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IL-10 Overexpression After BCG Vaccination Does Not Impair Control of Infection.BCG 疫苗接种后白细胞介素-10 过表达并不损害感染控制。
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TOLLIP Optimizes Dendritic Cell Maturation to Lipopolysaccharide and .TOLLIP 优化树突状细胞对脂多糖的成熟。
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早期的白细胞介素 10 促进了与血管相关的不能控制结核分枝杆菌感染的 CD4+T 细胞。
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Association of IFN-gamma and IL-10 gene variants with the risk of extrapulmonary tuberculosis.干扰素-γ和白细胞介素-10基因变异与肺外结核病风险的关联。
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Biosci Rep. 2020 Aug 28;40(8). doi: 10.1042/BSR20193141.
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Evaluation of TLR2, TLR4, and TOLLIP polymorphisms for their role in tuberculosis susceptibility.评估TLR2、TLR4和TOLLIP基因多态性在结核病易感性中的作用。
APMIS. 2018 Jun;126(6):501-508. doi: 10.1111/apm.12855.
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A Functional Toll-Interacting Protein Variant Is Associated with Bacillus Calmette-Guérin-Specific Immune Responses and Tuberculosis.一种功能性Toll相互作用蛋白变体与卡介苗特异性免疫反应及结核病相关。
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