The Role of Inflammatory Gene Polymorphisms on Risk of Post-Stroke Vascular Dementia (I)

Ischemic stroke is a major cause of disability and mortality worldwide. Poststroke cognitive decline is more common than stroke recurrence and stroke considerably increases the likelihood of dementia. Currently, vascular cognitive impairment (VCI) is a relatively new concept characterizing all possible cognitive levels of deficit presented after a stroke. VCI is classified as vascular mild cognitive impairment (VaMCI) and vascular dementia (VaD), based on functional impairment and number of evaluated cognitive domains. Recent researches have found that inflammation can cause VaD/VCI. However, little is known about the genetic effects of inflammation related variants on the risk of VaD/VCI after stroke. Thus, to identify the genetic variations of individual susceptibility on inflammation become the critical key to improve the risk of VaD/VCI and can provide promising avenues for strategies of prevention and therapy. The study population will expect to recruit 50 VaD ischemic stroke patients, 100 VaMCI ischemic stroke patients, 150 non-VCI ischemic stroke patients and 150 frequency-matched age and sex healthy subjects (normal control group) without cardiovascular disease. A structure questionnaire will be used to collect life style, environmental risk factors and disease histories from all subjects. All ischemic stroke patients will be followed up at 3months and 1 year after stroke onset and their cognitive status will be assessed by MoCa tset and MRI. Blood samples will be collected within 7 days and at 3 months and 1year after stroke. For controls, it will be collected 8 ml fasting peripheral blood samples and 8 ml whole blood with RNAlater during the health examination. We will use whole exome sequencing to test the hypothesis that inflammation related variants are significantly associated with VaD/VCI in humans. In addition, we will confirm the relationship between inflammation related variants and gene expression. The phenotype of interested genes will be assayed by ELISA kits or Q-PCR. To validate our findings, we will use iPLEX for genotyping an additional subjects of 1000 ischemic stroke patients (including VaD ischemic stroke patients, VaMCI ischemic stroke patients and non-VCI ischemic stroke patients) and 1000 healthy controls for the candidate inflammation related variants. Because only few studies explore the relationship between the genes of inflammation and VaD/VCI after stroke onset in humans, in this three-year project, we aim to (1) discover novel inflammatory gene polymorphisms related to risk of VaD/VCI after stroke by the whole exome sequencing; (2) evaluate the association between genetic polymorphisms of inflammation and risk of VaD/VCI after stroke; (3) investigate the interaction between traditional cardiovascular risk factors and genetic polymorphisms of inflammation on the risk of VaD/VCI after stroke.