|
The occurrence of thrombotic disease is the result of joint action by a variety of genetic and environmental factors. vWF multimeric glycoprotein synthesized by vascular endothelial cells and megakaryocytes, both start in a high shear state platelet adhesion, aggregation, and is portable coagulation factor VIII vectors, many recent in vitro experimental evidence, vWF in plays a key role in thrombosis. The study showed that, vWF is a risk factor for myocardial infarction occurs frequently in the general population of vWF gene promoter region-1051G / A,-1792C / G, etc. by adjusting the level of plasma vWF polymorphisms and ischemic heart disease closely related, the the vWF polypeptide sequence in Thr789Ala polymorphism of coronary heart disease in patients with type I diabetes as a risk factor. Reason as thrombosis candidate factor. Gene chip technology in gene sequencing, gene mutation and polymorphism analysis, gene expression and functional analysis, applications and library screening, the development of new drugs, and pathogen detection, showing broad application prospects. Single nucleotide polymorphisms (single nucleotide polymorphism, SNP) is the most common genetic variation variation in the human genome, the frequency of 0.5 to 10 per 1000bp. Very complex interactions between multiple genes and the environment, must be large numbers of the population SNP determined, in order to explain their role in the development of disease. Of this study was to investigate the vWF gene Rsa I, Sma Ⅰ polymorphism and thrombotic diseases occur whether the relationship; explore and gene chip technology for SNP detection. Study, we first establish of vWF gene Rsa Ⅰ, Sma I polymorphism oligo nucleotide array detection method. Design and synthesis of two sets of oligonucleotide probes, the use of 3-methoxy-aminopropylsilane, glutaraldehyde and other chemical substances, and the connection of the probe and the solid phase support slides. Application of asymmetric PCR methods Rsa Ⅰ, Sma Ⅰ polymorphic fragment was amplified in the amplification system, the incorporation of fluorescently labeled dUTP, measured fragment of single-chain labeled product. Nucleic acid hybridization reaction temperature, dynamics, and ion concentration changes obtained Best Hybrid identify conditions, randomly selected 20 normal digestion method to determine the genotypes, then oligonucleotide array method detection to verify the accuracy of the method. Using the method of detection of 50 cases of thrombosis patients, to investigate the occurrence of thrombotic diseases vWF gene Rsa I Sma I polymorphism relationship. The results showed that the oligonucleotide array method and digestion method of detection of 20 specimens was 100%; polymorphism genotypes between thrombosis patients and normal the two Suzhou University Fu degree thesis Chinese summary point and allele frequency differences were not statistically significant (P> 0.05). Therefore, this study successfully established the vWF gene Rsa Sma polymorphism oligonucleotide array detection of nuclear bitter acid to provide a basis for the application of gene chip technology in SNP detection; efficient diagnosis of genetic disease pathways also successful exploration; not been clear evidence that Rsa, Sma polymorphism related to the occurrence of thrombosis. In the study, 50 cases of thrombosis between patients and normal the Sma polymorphism differences in gene frequency and genotype distribution without significant statistical significance, however, the frequency of occurrence of thrombosis in patients Sma positive homozygous for normal people 2.7 times. In order to clarify this polymorphism thrombosis exact impact, we have expanded the number of sample cases and the use of inexpensive polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) technology instead of oligonucleotide bitter acid array detection method, in 107 patients with acute cerebral infarction (cerebral infarction), 53 cases of cerebral infarction in 49 patients with acute myocardial infarction (MI) patients and 113 normal controls, detection vWF gene Sma polymorphism, and which come from the same hospital 22 cases of myocardial infarction patients and 47 normal controls carried Determination of plasma vWFkg. In Sma polymorphic loci vAF gene genotype and allele distribution of cerebral infarction patients and normal control group, the difference was statistically significant ① The. OD households 0. om; O. 05> household 0.02 of which S. al positive homozygotes (CC) patients with cerebral infarction risk increased 3.29 times (0R == 3.29 95% CI: 1.5 7.01,0 m dam 0.001 MI genotypes and allele distribution between patients and normal control group no significant difference in significance (0.50> p) 0.30; 0.30> p> 0.20). Plasma vWFhg measurement results for normal subjects and cerebral infarction, myocardial infarction the patient plasma VWFkg level respectively 0.468,0.584 and 0.783U puzzle l. No significant difference between patients with cerebral infarction and control (peo.195 and myocardial infarction, a significant difference (p = 0.00 person v sipping genes Sma polymorphic loci genotype distribution in patients with normal control brain stem myocardial infarction patients and normal levels of plasma VWF Ag no mutual relationship (P = 0.323, P = 0.315, peo.96 people that the vWF gene Sma polymorphism associated with the incidence of cerebral infarction, may be one of the risk factors for the incidence of cerebral infarction; not found and related to the incidence of acute myocardial infarction; independent of the polymorphic loci with plasma vWFkg level. platelet thrombosis arterial thrombosis plays a very important role in selecting the appropriate antibodies, snake venom, synthetic peptides, and other substances, effectively inhibit platelet function, has become an effective way for the development of new antithrombotic drugs and anti-GP 11b/Illa monoclonal antibody 7E3 prepared parents - mouse chimeric antibody the hab fragment C7E3 , can significantly reduce the acute coronary syndrome after PTCA. incidence of reinfarction and ischemic complications have been approved by the FDA, and is widely used in the treatment of patients with ischemic heart disease. SZ my room prepared a GPIb a monoclonal antibody, the epitope is located in GPIb a Try276-Gin282, not only inhibit the ristocetin Voto?
|