糖原合成酶激酶-3β基因多态性、生活事件与重性抑郁障碍的相关性研究

发布时间：2018-03-22 13:38

本文选题：重性抑郁障碍　切入点：糖原合成酶激酶-3β　出处：《天津医科大学》2014年硕士论文　论文类型：学位论文

【摘要】：目的：重性抑郁障碍(MDD)是一种常见的慢性复发性精神疾病,严重的危害人类健康。近年来病因学研究证实MDD发生与遗传、环境因素密切相关,但其发病机理复杂,至今尚未完全阐明。糖原合成酶激酶-3β(GSK-3β)是调节神经生长与神经可塑性的重要因素,研究显示GSK-3β在MDD的病理生理和抗抑郁作用机制上发挥重要作用。本研究旨在探讨GSK-3β基因多态性与MDD发病、严重程度以及临床症状之间的关系,分析GSK-3β基因型和生活事件交互作用对MDD发病的影响,为其病理生理机制提供新的理论依据。方法：采用病例-对照研究方法,严格按照DSM-IV诊断标准,选取500例MDD患者和550例与之性别、年龄相匹配的正常对照作为研究对象。选用HAMD-17评定抑郁的严重程度,同时采用生活事件量表(LES)对两组的生活事件进行评定。实验中抽取被试外周静脉全血,提取基因组DNA,采用限制性片段长度多态性-聚合酶链反应(RFLP-PCR)技术对GSK-3β基因上的rs334558单核苷酸多态性进行分型。运用SPSS19.0统计软件包进行数据分析。结果： 1.GSK-3p基因rs334558位点基因型有CC、CT、TT三种多态性。经拟和优度χ2检验,病例组和对照组各基因型观察值与期望值间差异均无统计学意义(P0.05),符合Hardy-Weinberg定律。 2.病例组和对照组GSK-3p基因rs334558位点基因型和等位基因分布差异均无统计学意义(P0.05)。按性别进行分层,结果显示基因型和等位基因的分布在女性中有统计学意义(P0.05),而在男性中差异无统计学意义(P0.05)。仅在女性中,CC基因型与TT基因型存在统计学关联(P0.05,OR=0.528,95%CI为0.323-0.861),CC基因型是MDD发病的保护性因素；T等位基因与C等位基因之间也存在统计学关联(P0.05,OR=1.363,95%CI为1.100-1.688),携带T等位基因患MDD的危险是C等位基因的1.363倍。 3.分析GSK-3β基因rs334558位点不同基因型在人口学资料包括性别、婚姻、家族史、年龄、首发年龄上的分布,差异均无统计学意义(P0.05)。 4.GSK-3β基因rs334558位点不同基因型在HAMD量表“精神性焦虑”这 -条目上的差异存在统计学意义(P0.05),而在其余条目及HAMD总分、迟滞因子、睡眠因子、焦虑/躯体化因子、Maier症状因子、核心因子的评分中差异均无统计学意义(P0.05)。 5.病例组LES总分高于对照组,且差异具有统计学意义(P0.05)。对病例组不同基因型的LES总分进行比较,差异无统计学意义(P0.05)。根据HAMD总分将病例组分为轻中度抑郁组和重度抑郁组,重度抑郁组LES总分明显高于轻中度抑郁组(P0.05)。 6.多因素Logistic回归模型分析显示生活事件、基因型之间不存在和MDD的发病相关的交互作用(P0.05)。结论： 1.GSK-3β基因rs334558位点多态性在MDD的发生过程中可能存在性别特异性,仅在女性患者中基因型和等位基因的分布存在统计学差异,因此推测该基因多态性可能与中国天津地区女性人群MDD的发病有关,CC基因型可能降低MDD发生的危险性,携带T等位基因可能增加MDD发生的危险性。 2.GSK-3β基因rs334558位点的基因型分布与MDD患者的性别、婚姻、家族史、年龄、首发年龄等一般资料无关。 3.GSK-3β基因rs334558位点基因多态性对MDD的抑郁严重程度、迟滞症状、睡眠、焦虑/躯体化症状、Maier症状、核心症状等均无影响,但可能与MDD的精神性焦虑症状有关联。 4.生活事件可能是MDD发病的一个危险因素,MDD患者在发病前比正常对照经历更多的生活事件,且生活事件能够增加MDD的严重程度,生活事件越严重,患者的抑郁程度越严重。 5.基因-环境交互作用的研究发现,GSK-3β基因rs334558位点不同基因型和生活事件对MDD的发病可能不存在交互作用。
[Abstract]:Objective:
Major depressive disorder (MDD) is a common chronic recurrent psychiatric diseases, serious harm to human health. In recent years, the etiology study confirmed that MDD occurrence and genetic, environmental factors are closely related, but its pathogenesis is complex, has not yet been fully clarified. Glycogen synthase kinase -3 beta (GSK-3 beta) is an important factor in the regulation of nerve with the growth of neural plasticity, studies show that GSK-3 beta plays an important role in the pathophysiology of MDD and the antidepressant mechanism. This study aimed to investigate the GSK-3 gene polymorphism and the pathogenesis of MDD, as well as the relationship between the severity of clinical symptoms, analysis of the impact of GSK-3 gene type and life event interaction on the pathogenesis of MDD. To provide a new theoretical basis for its pathophysiological mechanism:
In a case-control study, in strict accordance with the diagnostic criteria of DSM-IV, a total of 500 cases of MDD patients and 550 patients with gender, age matched normal control as the research object. The severity assessment of HAMD-17 depression, and the life events scale (LES) were assessed in two groups of life events. In the experiment of extraction the subjects of peripheral venous blood, extract genomic DNA, using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) typing of single nucleotide polymorphism of rs334558 GSK-3 gene on technology. Packet data were analyzed by SPSS19.0 statistical software:
The genotype of rs334558 locus of 1.GSK-3p gene has three polymorphisms of CC, CT and TT. There was no significant difference between the observed values and the expected values of genotypes between the case group and the control group (P0.05), which was in accordance with Hardy-Weinberg law by the quasi goodness of fit 2 test.
2. in case group and control group GSK-3p rs334558 gene distribution difference of genotype and allele were not statistically significant (P0.05). Divided by sex, the results showed that the distribution of genotypes and alleles were statistically significant in women (P0.05), but there was no significant difference in men (P0.05). In women, CC and TT genotype was significantly associated (P0.05, OR=0.528,95%CI, 0.323-0.861) CC genotype is a protective factor in the pathogenesis of MDD; there is also a statistical association between T alleles and C alleles (P0.05, OR= 1.363,95%CI, 1.100-1.688) carrying dangerous T allele with MDD it is 1.363 times of the C allele.
3., there was no significant difference in the distribution of rs334558 genotype of GSK-3 beta gene in demographic data, including gender, marriage, family history, age and first age (P0.05).
The different genotypes of the 4.GSK-3 beta gene rs334558 loci are in the HAMD scale "mental anxiety"
The difference in items was statistically significant (P0.05), but there was no statistically significant difference in other items and HAMD total score, such as sluggish factor, sleep factor, anxiety / somatization factor, Maier symptom factor and core factor score (P0.05).
5. cases of group LES score higher than the control group, and the difference was statistically significant (P0.05). The cases of different genotypes of LES scores were compared, the difference was not statistically significant (P0.05). According to the HAMD scores of the patients were divided into mild to moderate depression group and severe depression group, severe depression group LES score was significantly higher than that of mild to moderate the depression group (P0.05).
6. multiple factor Logistic regression model analysis showed that there was no interaction between the genotypes and the pathogenesis of MDD (P0.05).
Conclusion:
1.GSK-3 gene rs334558 polymorphism may have gender specificity in the process of MDD, there were significant differences in the distribution only in female patients with genotype and allele, suggesting that this gene polymorphism may be associated with the incidence of female population in Tianjin area Chinese MDD, CC genotype may reduce the risk of MDD the T allele may increase the risk of MDD.
The genotype distribution of the 2.GSK-3 beta gene rs334558 loci is independent of the general data of sex, marriage, family history, age, and the first age of the MDD patients.
The rs334558 polymorphism of 3.GSK-3 beta gene has no effect on the severity of depression, delayed symptoms, sleep, anxiety / somatization symptoms, Maier symptoms and core symptoms of MDD, but it may be related to the mental anxiety symptoms of MDD.
4., life events may be a risk factor for the onset of MDD. MDD patients experience more life events before onset than normal controls, and life events can increase the severity of MDD. The more severe life events, the more severe the patients' depression is.
The study of 5. gene - environmental interaction has found that different genotypes and life events at the GSK-3 beta gene rs334558 locus may not interact with the pathogenesis of MDD.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R749.4

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