A single nucleotide polymorphism in hsa-miR-146a is responsible for the development of bronchial hyperresponsiveness in response to intubation during general anesthesia

Abstract

Bronchial hyperresponsiveness (BHR) is the most common clinical manifestation identified in asthmatic patients, and intubation is the major factor that stimulates the airway of patients receiving general anesthetic. In the present study, nitric oxide synthase 1 (NOS1) was identified as a target gene of micro (mi)R-146a using in silico analysis and luciferase assay. Furthermore, the regulatory role of miR-146a was demonstrated by the observation that the NOS1 expression level in pulmonary artery smooth muscle cells (PASMCs) transfected with miR-146a mimics was significantly downregulated and the NOS1 expression level in PASMCs transfected with miR-146a inhibitors was significantly upregulated. Additionally, it was identified that a polymorphism in pri-miR-146 interfered with mature processing and reduced the quantity of mature miRNA. To assess the association between the polymorphism and the development of BHR, 563 patients with basic pulmonary diseases, such as asthma, emphysema or bronchitis were enrolled in the present study. Each participant Received a general anesthetic and the development of BHR was evaluated. The miR-146a rs2910164 polymorphism CC genotype was identified to be significantly associated with an increased risk of BHR in response to intubation when compared with the GG or GC genotype (odds ratio, 0.38; confidence interval, 0.18-0.78). These findings indicate that the miR-146a rs2910164 polymorphism is associated with a decrease risk of BHR, and the CC genotype increased the level of NOS1 expression, which was physiologically inhibited by wild-type miR-146a.