| According to the statistics provided by the Office of Stoke Prevention and Screening of the People's Republic of China,China's cerebrovascular disease is second only to malignant tumors in urban and rural disease deaths in 2014.The age-standardized morbidity and mortality rates were 270/100 000,89/100 000,respectively,and those were 161/100 000,61/100 000 respectively.If this is the case,there will be more than1.5 million new cases of stroke each year,more than 1 million deaths,500-600 million survivors,and about 75% of survivors with varying degrees of disability,And society to bring a huge burden and influence.In the United States,there are about 700,000 new cases of stroke per year,of which about 200,000 people are recurrent,and about270,000 patients die with stroke,second only to heart disease and cancer.Brain stroke can be divided into ischemic stroke and hemorrhagic stroke,which is a major threat to human health and life.It's the third cause of death in the western population,age standardized incidence is 300-500/100 000 and mortality,second only to heart disease and malignant tumor.In China,the age standardized incidence of brain stroke is 120-180/100 000,and mortalityis 80-120/l00 000,became the first cause of death than malignant tumor.There are many causes of brain stroke,highe blood pressure,high cholesterol levels and smoking are the three main risk factors.Other causes of brain stroke include age,alcohol consumption,high blood sugar,reduced exercise capacity,etc.However,many studies have found that many people do not have a stroke,even if they have all kinds of risk factors,which indicates that the occurrence of stroke is also related to other factors,which needs further research.Both genetic factors and environmental factors may cause ischemic cerebrovascular disease,CYP1A1 gene polymorphism is considered to be associated with a variety of diseases.Previous studies have reported that CYP1A1 gene polymorphisms are associated with the production of vasoconstrictor substances derived from arachidonic acid and suggest that CYP1A1 activity may be associated with ischemic stroke in patients with essential hypertension.In addition,the presence of multiple genotypes may be related to the interaction between the CYP1A1 gene polymorphism and the gene.This study will examine the correlation between CYP1A1 gene polymorphism and the risk of ischemic stroke in Chinese population and the effect of gene interaction on the risk of CYP1A1 gene polymorphism in ischemic stroke in order to identify Ischemic stroke occurs in the CYP1A1 gene polymorphism SNP site.A micro Ribonucleic acid,mi R-497 can be found in brain tissue.Experiments shows that the expression of mi R-497 in brain tissue of mice with focal cerebral ischemia-reperfusion injury was significantly higher than that of normal tissues,Another experiment also found in hypoxia-reoxygenation injury brain tissues,the expression of mi R-497 in neurons was also significantly increased.In addition,further animal experiments confirmed that the expression level of mi R-497 was related to the volume of cerebral infarction and the severity of neurological deficit.By inhibiting the expression of mi R-497,the infarct volume of ischemia-reperfusion mice could be effectively reduced.Further experiments have shown that the mechanism is mainly mediated by inhibition of neuronal cell apoptosis.However,there is no research on the effect of serum mi R-497 on stroke recurrence and death in patients with acute ischemic stroke.For the above purposes,we conducted two studies.To investigate the role of CYP1A1 gene polymorphism in the prediction of ischemic stroke,and to explore the effect of CYP1A1 gene polymorphism on the risk prediction of ischemic stroke in patients with stroke and healthy population.(GMDR)method was used to investigate the relationship between allele-gene interaction and ischemic stroke risk.In addition,serum miR-497 levels were measured in patients with acute ischemic stroke.Baseline serum mi R-497 levels were measured.Pearson's correlation analysis was used to assess the relationship between mi R-497 levels and the severity of neurological deficits.ROC curve analysis was used to assess the value of serum mi R-497 expression in predicting the recurrence of stroke.According to the quartile of serum mi R-497 expression,acute ischemic stroke was divided into 4 groups.Kaplan-Maier survival curve was used to analyze the morbidity and log-rank test.One factor Cox regression model was used to assess the risk factors of ischemic stroke recurrence,and the confounding factors were corrected to analyze whether the expression level of serum mi R-497 was an independent predictor of adverse events.Part ?A retrospective case control study was conducted on the healthy population of patients with previous stroke,using DNA probes and genotyping methods,to explore the role of CYP1A1 gene polymorphism in the risk prediction of ischemic stroke.And generalized multifactor dimensionality reduction(GMDR)was used to analyze the gene-gene interaction.The results showed that in the community population in Shenzhen,age is still an independent risk factor for stroke onset,and the risk of hemorrhagic stroke and ischemic stroke increased gradually with age.Logistic regression analysis demonstrated hypertension,atrial fibrillation,dyslipidemia,diabetes,family history of stroke,overweight,little physical activity,drinking and smoking are significant correlation with brain stroke.Logistic regression analysis showed that the frequency for rs4646903 minor alleles were lower in cases than that in normal controls,C allele of rs4646903 was 20.7% in ischemic stroke cases and 27.1% in controls subjects(p<0.001).Logistic analysis showed the significant association between genotypes of variants in rs4646903 and decreased ischemic stroke risk.GMDR analysis indicated that there was a significant two-locus model(p=0.0107)involving rs4646903 and rs1048943,indicating a potential gene–gene interaction between rs4646903 and rs1048943.Overall,the two-locus models had a cross-validation consistency of 9 of10,and hadthe testing accuracy of 60.72%.Subjects with TC or CC of rs4646903 and AG or GG of rs1048943 genotype have lowest ischemic stroke risk,compared to subjects with TT of rs4646903 and AA of rs1048943 genotype,OR(95%CI)was 0.63(0.42-0.89).By analysis of the results,the prevention of stroke can be carried out by drugs,diet regulation,behavior intervention and other means to avoid risk factors,can play a role in reducing the incidence of stroke in high-risk groups.The polymorphism of CYP1A1 can reduce the risk of ischemic stroke in high risk groups,and has a certain guiding role in the prevention and treatment of ischemic stroke.Part ? We selected 130 patients who were diagnosed with acute ischemic stroke and 100 healthy volunteers were enrolled prospectively.Mi R-497 in the blood samples were analyzed using real-time PCR at baseline.The study endpoint was defined as all-cause death and recurrence of ischemic stroke including readmission.Receiver Operating Characteristic(ROC)Curve was applied for predicting negative outcome of.Kaplan-Meier statistics and multivariable Cox proportional hazard analysis were performed to study the association of baseline mi R-497 with adverse outcomes.Serum concentration of mi R-497 tended to increase with severity of neurologic impairment.During the median follow-up of 18 months(7.4-16.0 months),15 patients died due to ischemic stroke.The ROC curve revealed that the area under the curve(AUC)of mi R-497 for predicting negative outcome of ischemic stroke was 0.72(95%CI: 0.60-0.83,P < 0.01),the optimal serum mi R-497 cut-off point for predicting negative outcome of ischemic stroke was 225pg/ml with a sensitivity of 69.6%,a specificity of55.8%.This amount also represented a positive predictive value of 67.9% and a negative predictive value of 55.8%.Kaplan-Meier statistics showed that the risk of adverse event was 5.75 fold(hazard ratio 5.75,95%CI 1.53-21.58,P=0.009),which increased in the highest quartile(>296pg/L)compared with the lowest quartile(<173pg/L).After adjustment for cardiac function parameters,Cox regression analysis revealed that serum mi R-497 was an independent predictor for adverse event in patients with ischemic stroke after myocardial infarction(hazard ratio2.78,95%CI 1.02-7.57,P=0.046).By analysis of the results,we found that circulating mi R-497 might be a novel biomarker and a predictor of adverse outcomes in patients with acute ischemic stroke. |
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