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Objective To investigate correlation between the rs12122341 polymorphism and ischemic stroke and its major subtypes in Chinese Han population.Methods The patients with ischemic stroke and matched healthy controls in Chinese Han population were enrolled.The rs12122341 genotype was detected by the improved multiple ligase detection reaction (iMLDR).Results A total of 776 patients with ischemic stroke (415 large artery atherosclerotic stroke and 361 small artery occlusive stroke) and 776 healthy controls were enrolled.Genotyping showed that only rs12122341 CC and CG genotypes were detected in all subjects,and no GG genotype was detected.There was no significant difference in frequencies of allele and genotype between the patient group and the control group.Multivariate logistic regression analysis showed that there were no significant correlations between rs12122341 polymorphism and ischemic stroke (odds ratio [OR] 1.482,95％ confidence interval [CI]0.641-3.421;P =0.447),large artery atherosclerotic stroke (OR 1.972,95％ CI 0.655-6.034;P=0.227),and small arterial occlusive stroke (OR 1.632,95％ CI 0.437-6.262;P =1.000).Conclusions There is no significant correlation between the rs12122341 polymorphism and risk of ischemic stroke and its major subtypes in Chinese Han population.
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Objective To investigate the influence of one kind of defective gene NOTCH3 (R90C) of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in proliferation of oligodendrocyte lineage cells HS683 and their related molecular mechanism.Methods (1) A pCMV-Sport6.0 was chosen as the expression vector and site-directed mutation was used to construct the mutant NOTCH3 (p.R90C) expression vector;eukaryotic cell transfection technique was used to respectively transfect the pCMV-Sport6.0 empty vector,wild NOTCH3 vector (p.NOTCH3) and mutant NOTCH3 (p.R90C) expression vector to HS683 cells (blank control vector group,wild NOTCH3 vector group,and mutant NOTCH3 vector group);the protein expressions of NOTCH3,p53,phosphorylated p53 and p21 were detected by Westem blotting.(2) Wild NOTCH3 vector group,mutant NOTCH3 vector group and mutant NOTCH3 vector+pifithrin-α group were divided,and after wild NOTCH3 vector (p.NOTCH3) and mutant NOTCH3 (p.R90C) vector transfection,the latter two groups were added 0 or 1 μmol/L pifithrin-α,respectively;CCK-8 assay was employed to test the proliferation oftransfected HS683 cells 24,48 and 72,and 96 h after transfection.Results (1) As compared with wild NOTCH3 vector group,mutant NOTCH3 vector group had significantly lower absorbance value 24,48 and 72 h after transfection (P＜0.05);72 h after transfection,wild NOTCH3 vector group and mutant NOTCH3 vector group had significantly higher NOTCH3 protein expression as compared with blank control vector group (P＜0.05),and mutant NOTCH3 vector group had significantly higher p53,phosphorylated-p53 and p21 protein expressions as compared with wild NOTCH3 vector group and blank control vector group (P＜0.05).(2) The absorbance value in the mutant NOTCH3 vector+pifithrin-α group was significantly increased as compared with that in the mutant NOTCH3 vector group 48,72 and 96 h after transfection (P＜0.05).Conclusion Mutation of NOTCH3 (R90C) may inhibit the proliferation of oligodendrocyte cell lineage via p53 dependent way,which might play a direct role in demyelination pathology of CADASIL caused by NOTCH3(R90C).