MTHFR基因启动子区CpG岛甲基化与精神分裂症的相关研究

发布时间：2018-03-15 10:46

本文选题：精神分裂症　切入点：DNA甲基化　出处：《重庆医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：研究背景精神分裂症是一种病因尚未明了的常见的精神类疾病，其全球发病率大约为1%。亚甲基四氢叶酸还原酶(methylenetetrahydrofolatereductase,MTHFR)基因是精神分裂症的一个相关基因。已有研究证实精神分裂症可能与MTHFR基因的突变以及同型半胱氨酸(Hcy)和叶酸代谢的紊乱有关。目前,相关的研究主要集中在MTHFR基因C677T和A1298C这两个多态性位点上，而MTHFR基因启动子区域CpG岛的甲基化状态是否会影响该基因的表达，从而影响MTHFR的活性，进而可能与精神分裂症的发生有关，目前国内外仍未见相关报道。目的探讨精神分裂症患者MTHFR基因启动子区域CpG岛的甲基化状态是否与精神分裂症的发生有关。方法本研究选择精神分裂症患者和健康的正常人各20例，并收集所有研究对象的血样，，经亚硫酸氢钠处理后，分别采用甲基化特异性PCR（Methylation specific PCR,MSP）和硫化测序PCR（Bisulfite sequencingPCR,BSP）检测MTHFR基因启动子区域CpG岛的甲基化状态。此外，本研究还检测了所有研究对象血清中Hcy的水平。结果 MTHFR基因启动子区域的CpG岛有3个位点存在部分甲基化，分别是第69、80和129位点。患者组MTHFR基因启动子区域CpG岛存在部分甲基化的比例（40%）比对照组（20%）高，但两组之间并无明显的统计学差异(P＞0.05)。患者组血清中Hcy的水平（27.69±7.92μmol/L）比对照组（23.26±5.26μmol/L）高，且两组之间存在明显的统计学差异(P=0.044)。此外，MTHFR基因启动子区域CpG岛的甲基化状态以及血清中Hcy的水平与性别和年龄的分布均无明显的统计学差异(P均＞0.05)。结论 MTHFR基因启动子区域CpG岛的第69、80和129位点存在部分甲基化。MTHFR基因启动子区域CpG岛的甲基化状态可能与精神分裂症的发生无关。精神分裂症患者血液中Hcy水平的升高可能与MTHFR基因启动子区域CpG岛甲基化状态的改变无关。MTHFR基因启动子区域CpG岛的甲基化状态以及血清中Hcy的水平不存在年龄和性别的差异。
[Abstract]:Research background. Schizophrenia is a common mental disorder whose etiology is still unknown. The global incidence rate is about 1%. Methylenetetrahydrofolate reductase (MTHFR) gene is a gene related to schizophrenia. Studies have shown that schizophrenia may be associated with mutations in the MTHFR gene and homocysteine cysts and folic acid generation. Xie's disorder is related. At present, The related studies focused on the two polymorphic loci of MTHFR gene C677T and A1298C, and whether the methylation of the CpG island in the promoter region of the MTHFR gene affected the expression of the gene and the activity of MTHFR. And then may be related to the occurrence of schizophrenia, there are still no reports at home and abroad. Purpose. To investigate whether the methylation status of CpG island in the promoter region of MTHFR gene in schizophrenic patients is related to the occurrence of schizophrenia. Method. In this study, 20 schizophrenic patients and 20 healthy controls were selected. Blood samples of all subjects were collected and treated with sodium bisulfite. The methylation status of CpG islands in the promoter region of MTHFR gene was detected by methylation specific PCR(Methylation specific PCR and PCR(Bisulfite sequencingPCRSPs respectively. In addition, the levels of Hcy in the serum of all the subjects were also detected. Results. There were three sites of partial methylation in CpG island of MTHFR gene promoter region, they were 69n80 and 129.The proportion of partial methylation in CpG island of MTHFR gene promoter in patient group was 40% higher than that in control group (20%). But there was no significant statistical difference between the two groups (P > 0.05). The serum Hcy level in the patients group was 27.69 卤7.92 渭 mol / L higher than that in the control group (23.26 卤5.26 渭 mol / L). There was significant statistical difference between the two groups (P < 0.044). There was no significant difference in the methylation status of CpG island in the promoter region of the MTHFR gene, the level of Hcy in serum and the distribution of sex and age (P > 0.05). Conclusion. The methylation status of CpG island in the promoter region of MTHFR gene may not be related to the occurrence of schizophrenia. The increase of Hcy level in blood of schizophrenic patients. The methylation status of CpG island in the promoter region of MTHFR gene and the level of Hcy in serum were not different in age and sex, which may be related to the change of methylation status of CpG island in promoter region of MTHFR gene.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：D919.3

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