Risk Prediction Study Of CD40 -1D>T Polymorphism And Stroke And Identification Of Differentially Expressed Genes Of Chd7 Gene Mutation Mouse Model

Stroke is the most common acute disease which is extremely harmful.It is a kind of disease which is caused by blood clogging,which leads to blood not supplying oxygen to the brain,causing nerve tissue damage due to anoxia,or injecting blood cells into the nervous tissue caused by cerebral vascular rupture.By the end of January 2017,there were more than 11 million stroke patients in our country,and about 2.4 million patients were added each year,and about 1.1 million patients died of stroke each year.Stroke can be divided into two major categories,ischemic stroke,hemorrhagic stroke,of which ischemic stroke accounts for about 80%.The study of family,twins and animal experiments showed that the genetic factor was an important risk factor for the occurrence of stroke.CD40/CD40L plays an important role in human immune response,inflammatory response and coagulation,and the CD40 gene is a potential risk factor for the occurrence of stroke.The CD40-1C>T single nucleotide polymorphic loci is located in the Kozak sequence of the CD40 gene,and studies showed that the mutation of the site affects the expression of CD40protein.A case-control study,with 498 stroke patients?338 ischemic stroke and 160 hemorrhagic stroke?and 498 healthy controls,was conducted in the Han Chinese population to evaluate the possible association of CD40-1C>T SNP with stroke and its subtypes.CD40-1C>T SNP was significantly associated with total stroke(P_adjusted=0.001,OR=1.41[95%CI=1.15-1.74]),ischemic stroke(P_adjusted=0.022,OR=1.33[95%CI=1.04-1.69])and hemorrhagic stroke(P_adjusted=0.017,OR=1.40[95%CI=1.06-1.86]).In meta-analysis,there was a significant association between CD40-1C>T SNP and ischemic stroke?P<0.00001,OR=1.39[95%CI=1.25-1.56]?yielding 1.39 per T allele copy.CHARGE syndrome is a rare disease with a prevalence rate of about1:10000.CHARGE syndrome is the main clinical symptoms of six of the first letter of English together named,including Colobome,Heart malformations,Atresia of the choanae,Retardation of growth,Genital hypoplasia and Ear abnormalities.67%of patients with CHARGE syndrome have Chd7 gene mutation,ENU mutation by Chd7 mutagenesis mouse model construction will appear a variety of symptoms are similar with human CHARGE syndrome,such as eye tissue defects,heart defects,slow growth and spinning and other characteristics,is a powerful tool for functional study of Chd7 gene and CHARGE syndrome.The differentially expressed genes from expression spectrum chip analysis were analyzed by quantitative real-time PCR analysis.The differentially expression trend of the 6 genes coincides with the expression spectrum chip data;the expressions of Cav1?Pde4b?Flt1 and Vldlr gene were up-regulated,when expressions of Shox2 and Myog gene were down-regulated.Three genes were significantly differentially expressed in homozygote mouse embryos.Among them,the expressions of Shox2 gene were significantly down-regulated?P<0.0001?,the expressions of Myog gene were also significantly down-regulated?P=0.0222?and the expressions of Myog gene were significantly up-regulated?P=0.0105?.These are the potential target genes of the Chd7 gene,and the specific mechanism of action needs to be further verified by the analysis of the phenotype and protein expression of the mice.