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Sp3 Gene's Organization And The Genetic Relativity With Multiple Sclerosis

Posted on:2004-05-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:A Y LinFull Text:PDF
GTID:1104360092987068Subject:Neurology
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Background Multiple sclerosis (MS) is a central nervous system autoimmune disease, but the cause of the disease is not yet complete clarified. Both genetic and environmental factors may influence susceptibility to the disease, the function of the heredity has already been affirmed. But even now people haven't discover a unique gene whichever to decide the development of MS or any one gene can cause MS, but Looking for the relativity of Sp3 and MS has become an important research direction to announce the mechanisms of the disease. Sp3 gene is one of the transcriptional factors, which belonging to Sp family. It has the same DNA binding site with Spl and is concerned with regulation of many genes. It activates many virus and mammalian cells' promotors through the binding with GC/GT box, deciding the efficiency and specificity of the transcription of promotor. Sp3 gene turning out both activating and repressing function, even to the same gene, it can also develop the different function in different period, and therefore has got the important meaning to numerous genes of human body. In 1996, the researchers discovered the deficient express of Sp3 gene existed in MS when they studied with a monozygotic twin by differential display method. Succedent clinical research proved the conclusion. The mechanism of the phenomena is still ambiguity, but it has aroused people's abroad attention.Objective To observe the existence of Sp3 gene deficient express in Chinese multiple sclerosis, and discuss the correlation between Sp3 and the clinical presentation and prognosis in MS. Try to find out the possible reasons that cause the deficient express of Sp3, and further reveal mechanism of MS.Methods In the first part, we collected the patients with definite MS, and extracted the total RNA from PBMC. The RT- PCR method was used to observe Sp3 deficient expression phenomenon in the MS. In the second part, semi-quantitative RT-PCR method was used to investigate interleukine 10 express in patients' PBMC, we further study the relationship between Sp3 deficient expression and the level of interleukine 10 express. In the third part we BLAST in the GenBank using the published Sp3 cDNA sequences, to estimate Sp3 gene organization and location in the chromosome. SSCP method was used to screen the nucleutide mutation of coding sequences inorder to compare patients with normal controls. Direct sequencing was used to sequence a MS patient's cDNA sequences including 21 to 2065 nucleutides.Results In the first part, in MS group, we found 33 cases of 56 got Sp3 positive results, the other 23 cases got negative results, the absent rate was of Sp3 was 41.1%; in normal control group, 5 cases of 35 got negative results, the absent rate was 8.6%; in OD group, 4 cases of 27 got negative results, the absent rate was 14.3%; in OID group, 3 cases of 20 got negative results, the absent rate was 15.0%. In OD/OID groups, the Sp3 express rate were a little above the normal control group, but without statistical significant (P>0.05). But there were significant difference between MS and control groups bystatistical analysis (P<0.01). Sp3 expresses or not in MS patients was irrelevant with the number of relapse times, the number of the focus and the course of the disease. 5 Cases with hormone treatment patients who underwent active and stable stage didn't change the express of Sp3 or not. Sp3 lack express group showed no different with express group in EDSS grade in active MS, but there was distinct different in stable MS according to statistical analysis(P<0.05). Devic disease is an independent disease, most of the doctors think it is subspecies of MS. It showed lower deficient rate of Sp3 than other patients. We included 15 cases of Devic disease in our research, 4 of 15 lose the express of Sp3; while other members in MS group, 19 of 41 lose the express of Sp3, we found that Devic disease had a lower deficient rate of Sp3, but when we compared them with other members in MS group, there were no significant different between the lose rate, the valu...
Keywords/Search Tags:multiple sclerosis, Sp3, transcriptional factor, interleukine 10
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