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基因变异和表达水平对肺结核易感性和临床表现的影响。

The effects of and gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis.

机构信息

Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Department of Tuberculosis, Anhui Chest Hospital, Hefei, Anhui, China.

出版信息

Front Immunol. 2024 Apr 16;15:1267624. doi: 10.3389/fimmu.2024.1267624. eCollection 2024.

DOI:10.3389/fimmu.2024.1267624
PMID:38690286
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11058845/
Abstract

Inflammatory cytokines have crucial roles in the pathogenesis of tuberculosis (TB), and interleukin (IL)-27 and IL-35 have a pro-inflammatory and anti-inflammatory effect on many diseases, including infectious diseases. Therefore, we evaluated the relationship between and gene polymorphism, expression levels, and pulmonary TB (PTB) susceptibility. Nine single-nucleotide polymorphisms (SNPs) in the gene (rs181206, rs153109, and rs17855750) and the gene (rs4740, rs428253, rs9807813, rs2243123, rs2243135, and rs568408) were genotyped by the SNPscan technique in 497 patients with PTB and 501 controls. There was no significant difference regarding the genotype and allele frequencies of the above SNPs in the and genes between patients with PTB and controls. Haplotype analysis showed that the frequency of the GAC haplotype in the gene was significantly decreased in patients with PTB when compared to controls ( 0.036). Stratified analysis suggested that the frequency of the rs17855750 GG genotype was significantly increased in patients with PTB with fever. Moreover, the lower frequency of the rs568408 GA genotype was associated with drug-induced liver injury in patients with PTB. The rs428253 GC genotype, as well as the rs4740 AA genotype and A allele, showed significant relationships with hypoproteinemia in patients with PTB. When compared with controls, the IL-27 level was significantly increased in patients with PTB. Taken together, gene variation might contribute to a protective role on the susceptibility to PTB, and and gene polymorphisms were associated with several clinical manifestations of patients with PTB.

摘要

炎症细胞因子在结核病 (TB) 的发病机制中起着至关重要的作用,白细胞介素 (IL)-27 和 IL-35 对许多疾病(包括传染病)具有促炎和抗炎作用。因此,我们评估了 和 基因多态性、表达水平与肺结核 (PTB) 易感性之间的关系。采用 SNPscan 技术对 497 例 PTB 患者和 501 例对照者的 基因(rs181206、rs153109 和 rs17855750)和 基因(rs4740、rs428253、rs9807813、rs2243123、rs2243135 和 rs568408)的 9 个单核苷酸多态性 (SNP)进行了基因分型。PTB 患者与对照组在 和 基因上述 SNP 的基因型和等位基因频率无显著差异。单体型分析显示,与对照组相比,PTB 患者 基因中的 GAC 单体型频率显著降低( 0.036)。分层分析表明,发热的 PTB 患者 rs17855750 GG 基因型的频率显著增加。此外,PTB 患者药物性肝损伤与 rs568408 GA 基因型的低频率相关。 rs428253 GC 基因型以及 rs4740 AA 基因型和 A 等位基因与 PTB 患者低蛋白血症显著相关。与对照组相比,PTB 患者的 IL-27 水平显著升高。综上所述, 基因变异可能对 PTB 的易感性起保护作用, 和 基因多态性与 PTB 患者的几种临床表现有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7225/11058845/a7fa1e02ff89/fimmu-15-1267624-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7225/11058845/a7fa1e02ff89/fimmu-15-1267624-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7225/11058845/a7fa1e02ff89/fimmu-15-1267624-g001.jpg

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白细胞介素-27通过激活自噬减轻结核分枝杆菌诱导的巨噬细胞损伤和炎症。
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