The Association of Toll-like Receptor-9 Gene Single-Nucleotide Polymorphism and AK155(IL-26) Serum Levels with Chronic Obstructive Pulmonary Disease Exacerbation Risk: A Case-Controlled Study with Bioinformatics Analysis

Toll样受体9基因单核苷酸多态性及AK155(IL-26)血清水平与慢性阻塞性肺疾病急性加重风险的相关性:一项病例对照研究及生物信息学分析

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Abstract

Background: 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 TLR9 (T1237C) SNP rs5743836 and serum levels of AK155(IL-26) with the exacerbation of COPD. Subjects: A total of 96 COPD patients sub-classified into two groups. Materials: 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. Methods: Genotyping for TLR9 rs5743836 (T1237C) polymorphism was performed using real time polymerase chain reaction (RT-PCR). AK155(IL-26) serum levels were determined using ELISA. Results: There is a significantly higher frequency of the mutant homozygous genotype (C/C) and the mutated C allele of TLR9 rs5743836 (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, p = 0.001, OR 1.83, 1.02 to 3.27, p = 0.041, respectively. In the exacerbated COPD group, there was a significant association between TLR9 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 (p = 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. Conclusions: Our results demonstrated a relation linking TLR-9 rs5743836 (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.

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