The Association Of Hyperhomocy Steinemia And The Key Synthase In Its Metabolism And MTHFR, CBS Gene Variation With Young Ischemic Cerebral Vascular Diseases

The association of hyperhomocy steinemia and the key synthase in its metabolism and MTHFR, CBS Gene variation with young ischemic cerebral vascular diseases Cerebrovascular disease is the main cause of death and deformity all over the world ,and the cerebral arterial thrombosis is about eighty percent of cerebrovascular disease. Besides,people who were hyperlipemia are younger and younger,and patients who had taken this disease in early stage were not with the dangerous factors such as hypertension,high blood lipid,diabetes mellitus,coronary heart disease,and drunk,smoking etc. No exact reason was obtained for 21%-31% of cerebral arterial thrombosis. Therefor, to study the new dangerous factor, especially the heredity factor is urgent for the prevention of the cerebral arterial thrombosis in youth。More and more pieces of evidence indicated that the independent dangerous factor of the arteriosclerosis and the complication of cerebrovascular disease is that the light or moderate increase of homocysteine (Hcy) in plasma. Recently,some research showed that independent dangerous factor of the cerebral arterial thrombosis might be Hhcy,this problem has been the hot spot in neurology domain internationally. Homocysteine(Hcy)is the middle metabolism products of acimetion in human body. It was known that the increase of Hcy concentration in blood ,just as the hyperhomocysteinemia was related with all kinds of arteriosclerosis vascular disease closely. Literature investigation proved that the cause of Hhcy might be:(1)Nutrition,such as deficiency of Folic Acid,VitB12,VitB6. (2) Genetic factor, such as mutations of MTHFR gene and CBS gene.(3)Others,such as sex,race,hypothyroidism,antiepileptic,bendopa,renal function lesion,age,drunk,and smoking,Coffee etc。In our research,we detected the Hcy level of cerebral arterial thrombosis of youth,and we proved that the mutation of key enzyme of Hcy metabolism was related with cerebral arterial thrombosis of youth by molecular genetics,clarified the episode reason of cerebral apoplexy, proved that the relation of the easy-infected degree of cerebral arterial thrombosis of youth and some definite genetic polymorphism,provided the theoretical basis for screening of high risk group and clinical therapy。The coding correlated proteins of 5,10-methylenetertrahydrofolate reductase( MTHFR)gene and cystathionine beta-synthase(CBS)gene are both the key enzymes of Hcy metabolism in human body. This is the very reason that it was the objective gene in our research. Specific contents as follows:1,Select C677T,A1298C sites from MTHFR gene,these sites were reported had some relations with cerebral apoplexy in1996,but this idea was disputed all the time. Large systematic swatch was not found in our country,and dispute was serious. CBS T833C/G919A sites have polymorphism,the mutation of these genes can cause the increase of Hcy concentration in plasma,so it was the candidate gene for cerebrovascular disease. In our research,we chose the youth of cerebral apoplexy as study objects,to give further proof for this problem,to make persuasion strongly,to get rid of correlative factors interference with Logistic factor regression analysis. In China,there is little research in this aspect,the main content of this study is to explore the Hcy concentration level of 100 youth of cerebral apoplexy,and the relativity of the four sites mutation with the cerebral apoplexy of youth。The cases in our study were all the patients in nerve internal medicine of China-Japan Union hospital of Jilin University from April in 2003 to December in 2004.The criterion of choosing were : ①According to Cerebrovascular disease diagnosis standard established in the forth national academic meeting of Cerebrovascula by Chinese physic academy, the oneswho were diagnosed as cerebral arterial thrombosis,and were all identified by CT or MRI.②The patients'ages were≤45. The exclusion standards were:①The patients of diseases of lung,liver,kidney,diabetes mellitus,embolism from heart,hypothyroid,Psoriasis,malignancy.②The ones with brain embolism,Lacuna cerebral infarction and TIA.③The ones had no first ,second or third grade blood relationship。Study methods:1. Mensurate the Hcy level of the accepters who were limosis and burthen with High Performance Liquid Chromatography detected by fluorescence,and obtained genetic DNA.2.Extended the 4 gene fragments with polymersae chain reaction (PCR),analyzed the genetic polymorphism of the 4 gene fragments with restriction fragment length polymorphism(RFLP).3.Combined with clinical data,checked up data with X2test ,risk analysis and Multinomial Logistic regression analysis with SAS Stat. Software, the quantified data showed as mean±std. Deviation,with P﹤0.05 as the significant difference limitation。Results showed that :①The Hcy level in plasma of the cases who were limosis and burthen were higher than the control group significantly,P<0.05.There was significant difference in the Hhcy check-out ratio between the cases and the control. Hhcy correlated with youth cerebral arterial thrombosis closely,P<0.01.②For C677T polymorphism sites of MTHFR gene, the distributing frequency of three alleles and two types of allele were different significantly between the cases and the control. The MTHFR677C→T mutation had close relationship with cerebral arterial thrombosis of youth. The mutations of MTHFRA1298C, CBS T833C,G919A sites had no difference with the control. It was showed that the three mutation sites had no direct relations with youth cerebral arterial thrombosis,but they all can cause the high level of homocysteine (Hhcy) in plasma。To sum up , after compared 100 cases of youth cerebral arterial...