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巴西亚马逊地区细胞因子基因多态性及其对活动性和潜伏性结核病的影响的关联。

Association of Cytokine Gene Polymorphisms and Their Impact on Active and Latent Tuberculosis in Brazil's Amazon Region.

机构信息

Virus Laboratory, Institute of Biological Sciences, Federal University of Pará, Belém 66075-110, Brazil.

出版信息

Biomolecules. 2023 Oct 18;13(10):1541. doi: 10.3390/biom13101541.

Abstract

Some genetic variations in cytokine genes can alter their expression and influence the evolution of (Mtb) infection. This study aimed to investigate the association of polymorphisms in cytokine genes and variability in plasma levels of cytokines with the development of tuberculosis (TB) and latent tuberculosis infection (LTBI). Blood samples from 245 patients with TB, 80 with LTBI, and healthy controls (n = 100) were included. Genotyping of the +874A/T, -174G/C, -590C/T, and -1082A/G polymorphisms was performed by real-time PCR, and cytokine levels were determined by flow cytometry. Higher frequencies of genotypes AA ( +874A/T), GG ( -174G/C), TT ( -590C/T), and GG ( -1082A/G) were associated with an increased risk of TB compared to that of LTBI ( = 0.0027; = 0.0557; = 0.0286; = 0.0361, respectively) and the control ( = <0.0001, = 0.0021; = 0.01655; = 0.0132, respectively). In combination, the A allele for +874A/T and the T allele for -590C/T were associated with a higher chance of TB ( = 0.0080; = 2.753 and < 0.0001; = 3.273, respectively). The TB group had lower levels of IFN-γ and higher concentrations of IL-6, IL-4, and IL-10. Cytokine levels were different between the genotypes based on the polymorphisms investigated ( < 0.05). The genotype and wild-type allele for +874A/T and the genotype and polymorphic allele for -590C/T appear to be more relevant in the context of Mtb infection, which has been associated with the development of TB among individuals infected by the bacillus and with susceptibility to active infection but not with susceptibility to latent infection.

摘要

一些细胞因子基因的遗传变异可以改变它们的表达,并影响(Mtb)感染的演变。本研究旨在探讨细胞因子基因多态性与细胞因子血浆水平的变异性与结核病(TB)和潜伏性结核感染(LTBI)发展之间的关系。纳入了 245 例结核病患者、80 例 LTBI 患者和 100 例健康对照者的血液样本。通过实时 PCR 对 +874A/T、-174G/C、-590C/T 和 -1082A/G 多态性进行基因分型,并通过流式细胞术测定细胞因子水平。与 LTBI(=0.0027;=0.0557;=0.0286;=0.0361,分别)和对照组(=0.0001,=0.0021;=0.01655;=0.0132,分别)相比,+874A/T 基因型 AA、-174G/C 基因型 GG、-590C/T 基因型 TT 和-1082A/G 基因型 GG 的出现频率更高,与 TB 风险增加相关。在组合中,+874A/T 的 A 等位基因和-590C/T 的 T 等位基因与 TB 的更高几率相关(=0.0080;=2.753 和<0.0001;=3.273,分别)。TB 组 IFN-γ 水平较低,IL-6、IL-4 和 IL-10 浓度较高。根据所研究的多态性,细胞因子水平在不同基因型之间存在差异(<0.05)。+874A/T 的基因型和野生型等位基因以及-590C/T 的基因型和多态性等位基因在 Mtb 感染的背景下似乎更为相关,这与感染杆菌的个体中 TB 的发展以及对活动性感染的易感性有关,但与对潜伏性感染的易感性无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6588/10605732/5f536e498546/biomolecules-13-01541-g001.jpg

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