Genetic Polymorphisms in microRNA and Risk of the Post-Thrombolytic Hyperglycemia in Acute Ischemic Stroke and Its Prognosis Study

Stroke is the third most common cause of death and the leading cause of adult disability in Taiwan. More than half acute ischemic stroke patients had hyperglycemia. Numerous studies demonstrated that post-thrombolytic hyperglycemia in acute ischemic stroke patients had unfavorable outcomes, especially for persistent hyperglycemia stroke patients. However, the mechanisms underlying post-ischemic glucose intolerance remain unclear. Recently, microRNAs (miRNAs) are a new class of small non-protein-coding RNAs that can post-transcriptionally regulate the expression of their target genes. The aberration in miRNA expression may play a critical role in various metabolic disorders, including hyperglycemia, diabetes mellitus, neurodegeneration, neurological disorders, and so on. Therefore, the purpose of this study is 1) to screen the whole-genome serum miRNA using miRNA microarray on post-thrombolytic hyperglycemia in acute ischemic stroke patients and their unfavorable outcomes; 2) to validate the function of candidate miRNA; 3) to study the association between the candidate miRNAs-related SNPs and hyperglycemia ischemic stroke and validate the function of the candidate miRNAs-related SNPs. This is a three-year project. In the first year, we will recruit 5 persistent normoglycemia and 5 persistent hyperglycemia ischemic stroke patients. We will screen the possible miRNAs which the mechanism underlying hyperglycemia (included the insulin signaling pathway, regulation of oxidative stress-, inflammation-, endothelial dysfunction-, apoptosis- and angiogenesis-related genes) among the above subjects using the miRNA PCR array. In the second year, we will validate the candidate miRNA expression using qRT-PCR and the transfection studies in the cell line model. In the third year, we will select and genotype the potential SNPs regulated by the candidate miRNAs among 515 persistent normoglycemia and 352 persistent hyperglycemia ischemic stroke patients from our established stroke biobank dataset which included 2500 stroke patients. We will analyze the association between these candidate SNPs and hyperglycemia ischemic stroke and its related outcomes. In addition, we will execute the genetic functional studies in the cell line model on the significant SNPs related to hyperglycemia ischemic stroke and its related outcomes. Through our efforts, we anticipate that the possible candidate miRNAs and their related SNPs will be identified, and targets might be employed as new targets for alternative strategies for the treatment as well as prognostic markers of hyperglycemia acute stroke in the future.