Association of MicroRNA-196a2 Variant with Response to Short-Acting β2-Agonist in COPD: An Egyptian Pilot Study

Chronic obstructive pulmonary disease (COPD) is a multifactorial chronic respiratory disease, characterized by an obstructive pattern. Understanding the genetic predisposition of COPD is essential to develop personalized treatment regimens. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that modulate the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules. Emerging evidences demonstrated the potential use of miRNAs as a disease biomarker. This pilot study aimed to investigate the association of the MIR-196a2 rs11614913 (C/T) polymorphism with COPD susceptibility, the clinical outcome and bronchodilator response to short-acting β2-agonist. Genotyping of rs11614913 polymorphism was determined in 108 COPD male patients and 116 unrelated controls using real-time polymerase chain reaction technology. In silico target prediction and network core analysis were performed. COPD patients did not show significant differences in the genotype distribution (p = 0.415) and allele frequencies (p = 0.306) of the studied miRNA when compared with controls. There were also no associations with GOLD stage, dyspnea grade, disease exacerbations, COPD assessment test for estimating impact on health status score, or the frequency of intensive care unit admission. However, COPD patients with CC genotype corresponded to the smallest bronchodilator response after Salbutamol inhalation, the heterozygotes (CT) had an intermediate response, while those with the TT genotype showed the highest response (p慢性阻塞性肺疾病（Chronic obstructive pulmonary disease, COPD）是一类多因素参与的慢性呼吸系统疾病，以阻塞性通气表型为主要特征。明确COPD的遗传易感性，对于制定个体化治疗方案至关重要。微小核糖核酸（MicroRNAs, miRNAs）是一类内源性非编码RNA，可通过与靶mRNA分子的序列互补作用，调控特定蛋白的表达水平。越来越多的研究证据表明，miRNAs有望作为疾病生物标志物应用于临床。本预实验研究旨在探讨MIR-196a2 rs11614913（C/T）多态性与COPD易感性、临床结局以及短效β2受体激动剂支气管舒张反应之间的关联。本研究采用实时聚合酶链反应技术，对108例男性COPD患者与116例无关健康对照的rs11614913多态性进行基因分型。同时开展了计算机靶基因预测与网络核心分析。与健康对照相比，COPD患者所研究的miRNA位点的基因型分布（p=0.415）与等位基因频率（p=0.306）均无显著差异。该多态性与COPD的全球慢性阻塞性肺疾病倡议分期（GOLD分期）、呼吸困难分级、疾病急性加重次数、用于评估健康状况影响的COPD评估测试（CAT）评分以及重症监护病房收治频率均无显著关联。然而，携带CC基因型的COPD患者在吸入沙丁胺醇后表现出最弱的支气管舒张反应，杂合子（CT型）的反应程度居中，而TT基因型患者则呈现出最强的支气管舒张反应（p