Genetic Polymorphisms in Hypoxia Inducible Factor-1 and Inflammation Pathway Related microRNA and Its Target Genes and Risk of 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 and lead to have unfavorable outcomes. However, the mechanisms are complex and remain unclear. Of those variety of complicated mechanisms, there is no studies investigating on the effect of HIF-1 on cerebral vascular inflammation in hyperglycemia ischemic stroke. Recently, microRNAs (miRNAs) are a new class of small non-protein-coding RNAs that can post-transcriptionally regulate the expression of their target genes. In addition, miRNA networks may be disturbed by polymorphisms in the miRNA regulatory pathway (miRSNPs). Both of them have the potential to serve as disease biomarkers. The purpose of this study is to investigate the relationship of HIF-1 and inflammation pathway related candidate miRNAs and miRSNPs and hyperglycemia ischemic stroke and its unfavorable outcomes. This is a three-year project. In the first year, we aims to discover the most promising miRNA of HIF-1 and inflammation pathway in hyperglycemia ischemic stroke. This is a two-stage project. In the training stage, we will validate 20 candidate miRNA expression between 20 persistent normal-glycemia and 20 persistent hyperglycemia ischemic stroke patients, which are from our previous study sponsored by the Ministry of Science and Technology and are all related to HIF-1 and inflammation pathway. We expect to filter out less significant miRNAs and acquire around 6 more promising miRNAs. In the validation stage, these 6 miRNAs will be examined between 100 persistent normal-glycemia and 100 persistent hyperglycemia ischemic stroke patients. We anticipate to acquire the most 3 significant miRNAs, In the second year, the specific aim is to study the association between the miRSNPs of the most 3 promising miRNAs related to HIF-1 and inflammation pathway in hyperglycemia ischemic stroke. We will conduct a genetic association study to investigate the association between these miRSNPs among 600 persistent normal-glycemia and 400 persistent hyperglycemia ischemic stroke patients. In the third yean the specific purpose is to validate the function of the most promising miRNAs and significant miRSNPs in vitro. We expect to discover the significant miRNAs and miRSNPs of HIF-1 and inflammation pathway as a prognostic biomarker of hyperglycemia ischemic stroke. Through our efforts, we anticipate that HIF-1 and inflammation related candidate miRNAs and miRSNPs will be identified, and expect these candidates might be employed as new targets for alternative strategies for the treatment as well as prognostic markers of hyperglycemia acute stroke in the future.