The Impacts of Sirtuin Related Genes and Aging Related Factors on the Risk of Early-Onset Ischemic Stroke

Stroke is the major leading cause of disability. About 20.9% ischemic stroke patients onset at the age less than 55 years old. Genetic factors play an important role on premature cardiovascular system dysfunction. In our previous study, we found that TERC rs12696304C allele and TRF1 rs2975843C allele were independent prediction factors of early-onset ischemic stroke. Recently, accumulating evidence from animal and cell models showed that the level of sirtuin expression was related to aging and age related diseases. However, few studies investigate the relationship between sirtuin and risk of early-onset ischemic stroke. Therefore, we aim to investigate the impacts of sirtuin related genes and aging related factors on the risk of early-onset ischemic stroke. In this project, a total of 500 early-onset ischemic stroke cases (age ^ 55 y/o) confirmed with computerized tomographic scan and/or magnetic resonance imaging will be recruited as cases and 500 participants from the health examination frequency-matched by age and sex with cases will be recruited as controls. The information of life style and biological risk factors will be collected from all study subjects through a structured questionnaire. Genotyping of sirtuin related genes (SIRT 1-7 and miRNAs) will be determined by the methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or iPLEX® Gold Mass ARRAY assay. The level of sirtuin expression in blood will be detected by ELISA. Weighted and unweighted genetic risk scores will be used to evaluate the effect of sirtuin related genes on the risk prediction model. This three-year project aims to 1) evaluate the association of sirtuin related genes (SIRT 1-7 and miRNAs) and the risk of early-onset ischemic stroke; 2) to explore the joint effect of gene-gene and gene-environment on the risk of early-onset ischemic stroke; 3) to validate the correlation between the genetic polymorphisms of sirtuin related genes (SIRT 1-7 and miRNAs) and the level of sirtuin expression in blood.