变应性鼻炎易感性相关miRNAs基因及其靶标3'UTR功能性SNPs的鉴定与功能验证

Allergic rhinitis is correlated with environmental exposures and individual genetic predisposition. Recent studies have found that microRNA target sequence of single nucleotide polymorphisms (SNP) loci act as a "switch" in the regulation of microRNA process. Our previous studies found that lung surfactant protein D (SP-D) loci of SNP rs721917 CC genotype group had 2.847 times higher risk of allergic rhinitis than the general population. We speculate that there may be some microRNA SNP affecting miRNA synthesis and maturation, regulating of target gene function, thus affecting the development and progression of allergic rhinitis. To confirm this hypothesis, the project intends to use bioinformatic prediction of target genes and target sequence SNP, qPCR and pyrosequencing verification to explore microRNA target sequences associated with single nucleotide polymorphism susceptibility to allergic rhinitis. From the perspective of miRNAs target sequence SNP, we could find susceptible key molecule to establish more effective targeted treatment strategies to understand the pathogenesis of allergic rhinitis.

变应性鼻炎的发生与环境及遗传因素有关。研究证实，微小RNA（microRNA）通过调节靶基因 mRNA 表达参与变态反应炎性过程，miRNA靶序列中单核苷酸多态性SNP位点在miRNA调控过程中充当"开关"的重要角色。我们前期研究发现肺表面活性蛋白D(SP-D)的SNP rs721917位点中，携带CC基因型的人群发生变应性鼻炎的风险较正常人群高2.847倍。我们推测miRNA可能存在某些SNP，通过影响miRNA的合成和成熟，调控靶基因的功能，从而影响变应性鼻炎的发生和发展。为证实该假设，本项目拟利用生物信息学预测miRNA的靶基因及其靶序列的SNP，qPCR及焦磷酸测序验证，探讨miRNA靶序列单核苷酸多态性与变应性鼻炎易感性的关联，拟从miRNAs靶序列单核苷酸多态性角度全新认识变应性鼻炎的发病机制，发现变应性鼻炎关键易感分子以建立更有效的针对性治疗策略。

变应性鼻炎的发生与环境及遗传因素有关。研究证实，微小RNA（microRNA）通过调节靶基因 mRNA 表达参与变态反应炎性过程，miRNA靶序列中单核苷酸多态性SNP位点在miRNA调控过程中充当"开关"的重要角色。我们前期研究发现肺表面活性蛋白D(SP-D)的SNP rs721917位点中，携带CC基因型的人群发生变应性鼻炎的风险较正常人群高2.847倍。我们推测miRNA可能存在某些SNP，通过影响miRNA的合成和成熟，调控靶基因的功能，从而影响变应性鼻炎的发生和发展。本研究通过生物信息学预测miRNA的靶基因及其靶序列的SNP，qPCR及焦磷酸测序验证，发现MAPK8的3’UTR区域内T突变为A增加了患过敏性鼻炎的几率，靶基因3‘UTR区域的单核苷酸多态性变异可能可以影响miRNA与靶基因的结合，并进而影响下游一系列细胞因子的表达，进而导致过敏性鼻炎症状的出现。