Association between lipid, glucose related genes and prognosis of intra- and extra-cranial stenosis in stroke patients

Ischemic stroke is a global health problem.The major subtype of ischemic stroke is large artery atherothrombosis (LAA). Depending on the lesion location, there were two different type of LAA, including intracranial and extracranial stenosis. The etiological mechanisms between intracranial and extracranial stenosis are unclear. Previous studies speculated that high lipid level or insulin resistane may result in different severity between intracranial and extracranial stenosis. Therefore, the aim of this project is to explore the role of lipid metabolism, glucose homeostasis, their inducible anti-oxidant and inflammatory related genes, and their phenotypes on risk, severity and prognosis of intracranial and extracranial stenosis. A total of 1800 LAA stroke patients, including 1500 intracranial stenosis and 300 extracranial stenosis patients, diagnosed with computerized tomographic (CT) scan and/or magnetic resonance imaging (MRI) will be recruited from seven participant hospitals (NTUH, SKH, WFH , CMMC, TSGH, NCKH, SHH and WFH). The information of life style, environmental risk factors and disease histories 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 and discharge. All patients will also be followed up at 1-, 3-, 6-month and 1-year after stroke onset and their functional status will be assessed by modified Rankin Scale. Genotyping of lipid metabolism, glucose homeostasis, anti-oxidant and inflammatory related genes will be determined by the methods of iPLEX, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time polymerase chain reaction (RT-PCR) respectively. The phenotypes of lipid metabolism and glucose homeostasis related genes will also be assayed by ELISA kits. The project is the first study to explore the association of lipid metabolism and glucose homeostasis related genes on risk of intracranial and extracranial stenosis in humans. This three-year project aims to 1) to evaluate the association of lipid metabolism, glucose homeostasis, their inducible anti-oxidant and inflammatory related genes, and their phenotypes on risk of intracranial and extracranial stenosis; 2) to investigate the correlation of lipid metabolism, glucose homeostasis, their inducible anti-oxidant and inflammatory related genes, and their phenotypes on stroke severity at admission and discharge; 3) to explore the relationship of lipid metabolism, glucose homeostasis, their inducible anti-oxidant and inflammatory related genes, and their phenotypes on stroke outcomes (functional status, recurrence, and mortality) at 1-, 3- ,6- month and 1-year after stroke onset. Through these specific aims, we will have study results to elucidate the different mechanism between intracranial and extracranial stenosis. Moreover, a preventive strategy to reduce risk of these two types of LAA will also be provided.