The association of early-onset ischemic stroke and the aging of vascular system using the telomere length related genes

Stroke is the third leading cause of death and an important source of disability in Taiwan. The majority of stroke is ischemic stroke. There is about 20.9% of ischemic stroke patient onset before 55 years old. Cardioembolism and premature atherosclerosis were the most two important factors related to the development of early-onset ischemic stroke. Recently, it has been reported that a dysfunctional telomere pathway may lead to impaired DNA damage repair, genomic instability, and ultimately, the initiation of atherosclerosis, which is one of the important causes of ischemic stroke in young adults. However, few studies investigate the relationship between the genetic polymorphisms of telomere length pathway genes, and the risk and severity of early-onset ischemic stroke. In this project, a total of 1000 early-onset ischemic stroke cases confirmed with computerized tomographic scan and/or magnetic resonance imaging will be recruited from seven hospitals (NTUH, SKH, CMMC, TSGH, TMUH, SHH and WFH). A total of 1000 healthy controls will be frequency-matched by age and sex with cases and recruited from the health examinations from SKH, TMUH, SHH and WFH. The information of life style and biological risk factors will be collected from all study subjects through a structured questionnaire. The NIH Stroke Scale will be used to determine the stroke severity at admission in cases. Genotyping of telomerase components (TER, TERT, and DKC1), shelterin proteins related to telomere length (TRF1, TRF2, POT1, TIN2, TERF2IP, and TPP1), and telomere maintenance (hEST1A, RPA1, and Ku70) will be determined by the methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or real-time polymerase chain reaction (RT-PCR). This three-year project aims to 1) evaluate the association of the risk of early-onset ischemic stroke and telomerase components (TER, TERT, and DKC1), shelterin proteins related to telomere length (TRF1, TRF2, POT1, TIN2, TERF2IP, and TPP1), and telomere maintenance (hEST1A, RPA1, and Ku70).; 2) to investigate the correlation between the telomere length pathway genes and early-onset ischemic stroke severity; 3) to explore the joint effect of gene-gene and gene-environment on the risk and severity of early-onset ischemic stroke; 4) to investigate the modify effect of telomere length pathway genes on the traditional cardiovascular risk factor to the risk and severity of early-onset ischemic stroke