课题组前期通过微小RNA（miRNA）筛选并验证高血压患者有3种miRNA异常表达，其中miR-511编码基因变异与原发性高血压存在显著关联，结果表明miRNA及其基因变异可能共同参与了高血压发病机制。最近国外研究提示，环状非编码RNA（circRNA）通过与miRNA交互作用参与了动脉粥样硬化病理机制，但circRNA与高血压、脑卒中关系的研究少见报道。本课题采用病例对照研究设计,宏观人群研究与分子遗传学研究相结合，通过筛选高血压及缺血性脑卒中与正常对照差异表达的circRNA，分析circRNA和编码基因变异与前期发现异常表达miRNA的关系及其对高血压、脑卒中发病的作用，应用广义多因子降维法（GMDR）分析基因-基因、基因-环境交互作用，结果将有助于系统阐明高血压和缺血性脑卒中的表观遗传学机制，为其临床治疗药物设计靶点提供思路和线索，并可为疾病预后评价和人群防制提供敏感指标理论依据。

Our previous study used microRNA (miRNA) chip to screen relevant miRNA for hypertension and vivificated 3 kinds of miRNA (miR-511, miR-520a-3p and miR-1274a) abnormal expression comparing to health control subjects. Further study showed that miR-511 polymorphism rs4748424 was significantly associated with essential hypertension. The results indicated that miRNA and encoding gene variation may be involved in the pathogenesis of hypertension. Recent studies supported that circular non-coding RNA (circRNA) played an important role in the pathomechanism of atherosclerosis with the interaction of miRNAs but there was rare study investigating the relationship between the circRNA and hypertension as well as stroke. The project would conduct a large sample size case-control study to screen the serum abnormal expressed circRNA relevant to hypertension and stroke and evaluate the association of the encoding genes of candidate circRNAs with hypertension and stroke by combining with the significant miRNA identified previously. In addition, the generalized multifactor dimensionality reduction (GMDR) analysis will be used to evaluate gene-gene and gene-environment interaction. The expected results of this study would be helpful to illuminate the epigenetic mechanism of circRNA involved in the pathogenesis of hypertension and stroke and provide sensitive biomarkers for evaluation of clinical prognosis of hypertension and stroke and theoretical basis for the screening of drug targets and disease prevention.