Toll样受体9基因单核苷酸多态性及血清水平与慢性阻塞性肺疾病急性加重风险的关联：一项生物信息学分析的病例对照研究

The Association of Toll-like Receptor-9 Gene Single-Nucleotide Polymorphism and Serum Levels with Chronic Obstructive Pulmonary Disease Exacerbation Risk: A Case-Controlled Study with Bioinformatics Analysis.

作者信息

Mokhtar Entsar R, Elshennawy Salwa I, Elhakeem Heba, Saleh Rayyh A M, Elsawy Sawsan Bakr, Salama Khadiga S M, Mohamed Maha Fathy, Bahi Rania Hamid, Mansour Hayam H, Kasim Mahmoud Sammar Ahmed, Hassan Marwa M, Elhadad Sara M, Eid El Sayed Hanaa Mohammed, Mohamed Aliaa N, Hamdy Nadia M

机构信息

Clinical Pathology Department, Faculty of Medicine (for Girls), Al-Azhar University, Nasr City, Cairo 11884, Egypt.

Chest Disease Department, Faculty of Medicine (for Girls), Al-Azhar University, Nasr City, Cairo 11884, Egypt.

出版信息

Biomedicines. 2025 Mar 3;13(3):613. doi: 10.3390/biomedicines13030613.

DOI:10.3390/biomedicines13030613

PMID:40149591

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11939906/

Abstract

A crucial challenge is the determination of chronic obstructive pulmonary disease (COPD) immune-related mechanisms, where one of the important components of the inflammatory axes in COPD is Toll-like receptor-9 (TLR9) and interleukin-26 AK155(IL-26). Aim: To examine the relation between (T1237C) SNP and serum levels of AK155(IL-26) with the exacerbation of COPD. Subjects: A total of 96 COPD patients sub-classified into two groups. DNA was purified from blood samples of stable COPD patients (n = 48) vs. exacerbated COPD patients (n = 48) as well as 42 age- and sex-matched healthy smokers and passive smokers as a control group. Genotyping for (T1237C) polymorphism was performed using real time polymerase chain reaction (RT-PCR). AK155(IL-26) serum levels were determined using ELISA. There is a significantly higher frequency of the mutant homozygous genotype (C/C) and the mutated C allele of (T1237C) in COPD patients and in the exacerbated group when compared with the control group and stable COPD patients, respectively, with OR 31.98, 1.8 to 57.7, and OR 3.64, 0.98 to 13.36, respectively. For the mutated C allele, the OR was 3.57, 1.94 to 6.56, = 0.001, OR 1.83, 1.02 to 3.27, = 0.041, respectively. In the exacerbated COPD group, there was a significant association between rs5743836 SNP and BMI and the lung vital function measures, CRP, and AK155(IL-26). The exacerbated COPD group has higher serum levels of AK155(IL-26) compared with the stable group or when compared with the control group ( = 0.001) for both. AK155(IL-26) serum levels have a positive significant correlation with CRP and BMI and a significant negative correlation with FEV1% and FEV1/FVC in exacerbated COPD patients. Our results demonstrated a relation linking (T1237C) expression and the risk of COPD development and its exacerbation, indicating that dysfunctional polymorphisms of the innate immune genes can affect COPD development and its exacerbation. AK155(IL-26) upregulation was related to decreased lung functionality, systematic inflammatory disease, and COPD exacerbation.

摘要

一个关键挑战是确定慢性阻塞性肺疾病（COPD）的免疫相关机制，其中COPD炎症轴的重要组成部分之一是Toll样受体9（TLR9）和白细胞介素26 AK155（IL-26）。目的：研究（T1237C）单核苷酸多态性（SNP）与AK155（IL-26）血清水平与COPD急性加重之间的关系。对象：共96例COPD患者分为两组。从稳定期COPD患者（n = 48）与急性加重期COPD患者（n = 48）的血样中提取DNA，以及42名年龄和性别匹配的健康吸烟者和被动吸烟者作为对照组。采用实时聚合酶链反应（RT-PCR）对（T1237C）多态性进行基因分型。采用酶联免疫吸附测定（ELISA）法测定AK155（IL-26）血清水平。与对照组和稳定期COPD患者相比，COPD患者及急性加重组中突变纯合基因型（C/C）和（T1237C）突变C等位基因的频率显著更高，其比值比（OR）分别为31.98（1.8至57.7）和3.64（0.98至13.36）。对于突变C等位基因，OR分别为3.57（1.94至6.56），P = 0.001；OR为1.83（1.02至3.27），P = 0.041。在COPD急性加重组中，rs5743836 SNP与体重指数（BMI）、肺通气功能指标、C反应蛋白（CRP）和AK155（IL-26）之间存在显著关联。与稳定组相比或与对照组相比，COPD急性加重组的AK155（IL-26）血清水平均更高（两者P均 = 0.001）。在COPD急性加重患者中，AK155（IL-26）血清水平与CRP和BMI呈显著正相关，与第1秒用力呼气容积百分比（FEV1%）和FEV1/用力肺活量（FVC）呈显著负相关。我们的结果表明（T1237C）表达与COPD发生风险及其急性加重之间存在关联，表明先天性免疫基因的功能失调多态性可影响COPD的发生及其急性加重。AK155（IL-26）上调与肺功能下降、全身炎症性疾病及COPD急性加重有关。