| Objective:Ischemic stroke(IS)is a common disease that poses serious risks to human life and health.Studies have shown that IS is influenced by environmental and genetic,among others,that make it difficult to control effectively.As a result,it has become crucial in the field of medicine to do research on IS to support its prevention and control.The function of genes in the incidence of IS,particularly the significance of micro RNAs in the mechanism of IS pathogenesis,has become a hot research subject as a result of the widespread use of gene-related technologies in the study of human diseases.miR-208 a is a member of the micro RNA family,which is involved in oxidative stress and inflammatory responses and plays a key role in the formation of atherosclerosis(AS).The formation of AS is the pathological basis of IS,therefore,miR-208 a may be involved in the development of IS.Our group searched the db SNP database and found that there are multiple genetic polymorphisms at miR-208 a loci,and it is unclear whether the genetic polymorphisms at these loci are correlated with IS.The rs8022522 locus,which has been scanned by the 1000 genomes project and has a minor allele frequency of >5% in Asian populations,was selected for a case-control approach to analyze its association with IS.In order to further explore the molecular mechanism of miR-208 a involvement in the pathological basis of IS development-atherosclerosis,human umbilical vein endothelial cells(HUVECs)treated with ox-LDL were used as a cell model of atherosclerosis to analyze the effect of up-or down-regulation of miR-208 a on We analyzed the effect of up-or down-regulation of miR-208 a on the apoptosis and viability of HUVECs as a model of atherosclerosis to promote a new understanding of the mechanism of IS vascular injury and thus provide new targets for IS gene diagnosis and treatment.Method:(1)A total of 242 cases and 230 control samples were collected and genomic DNA was extracted.The SNPscan technique was used to detect the distribution of rs8022522 polymorphic loci in the two groups and analyze their correlation with IS.(2)Thirty samples were randomly collected from each of the IS and control groups.miR-208 a gene expression in peripheral blood single nuclei was detected by RT-q PCR.(3)HUVECs were treated with 100 μg/m L of ox-LDL to construct an atherosclerotic cell model;combined with RT-q PCR,CCK-8 and flow cytometry to investigate the molecular mechanism of miR-208 a involvement in IS and probe the mechanism of atherosclerotic vascular injury in IS.Result:(1)SNPscan genotyping results showed that the miR-208 a gene rs8022522 locus was present in AA,AG and GG genotypes in both the case and control groups.(2)The risk of IS was significantly higher in individuals carrying the AA and GA genotypes compared with the GG genotype(GG vs.GA OR=1.652,95%CI,1.085-2.517,P<0.05;GG vs.AA OR=2.602,95% CI,1.126-6.011,P<0.05);further analysis of the model revealed that the dominant model significantly increased the risk of developing IS(AA+GA vs.GG: OR=1.786,95% CI,1.203-2.651,P<0.05);the expression of miR-208 a in peripheral blood individual nuclei was significantly higher in the ischemic stroke group than in healthy controls(P<0.05).(3)When compared to the control group,the atherosclerotic cell model had higher levels of miR-208 a expression(P<0.05).In the atherosclerotic cell model,up-regulation of miR-208 a expression level decreased HUVECs viability and increased their apoptosis,while down-regulation of miR-208 a expression level increased HUVECs viability and decreased their apoptosis(P<0.05).Conclusion:(1)There is a genetic polymorphism at the rs8022522 locus of miR-208 a gene.(2)The miR-208 a gene rs8022522 locus polymorphism was associated with genetic susceptibility to IS.(3)The miR-208 a expression in peripheral blood individual nuclei of IS patients was higher than that of healthy controls,which may be a potential biological marker or therapeutic target for ischemic stroke.(4)miR-208 a has potential atherosclerosis-promoting effects. |
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