FKBP5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：2018-04-03 09:34

本文选题：重性抑郁障碍　切入点：FKBP5　出处：《天津医科大学》2014年硕士论文

【摘要】：目的：下丘脑-垂体-肾上腺轴(HPA轴)功能异常以及糖皮质激素(GC)持续升高被认为是引起重性抑郁障碍(MDD)的主要原因之一,且FKBP5为HPA轴反应性以及GC敏感性的重要调整者。从分子生物学水平探索FKBP5基因rs1360780位点多态性与MDD的发病、临床表型之间的关系以及与生活事件的交互作用对MDD发病的影响,进一步研究MDD的发病机制,为筛选危险人群、早期诊断、早期干预及个体化治疗提供理论依据,为新型抗抑郁药物的研发提供新思路。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。采用HAMD-17评定MDD的严重程度,同时采用生活事件量表(LES)对病例组和对照组的生活事件进行评定。抽取被试外周静脉全血,提取基因组DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对FKBP5基因上的rs1360780位点多态性进行分型。运用SPSS17.0统计软件包进行数据分析,P小于0.05为差异有统计学意义。结果： 1、FKBP5基因rs1360780位点有三种基因型CC、CT和TT。病例组和对照组中各基因型分布频率与期望频率的差别没有统计学差异,符合Hardy-Weinberg定律。 2、病例组和对照组FKBP5基因rs1360780位点各基因型和等位基因频率的分布差异在男性中均有统计学意义(P0.05),并且携带T等位基因的人群患MDD的危险度是携带C等位基因的1.608倍(OR=I.608,95%CI1.095～2.360)；而在整体样本中或女性中各基因型及等位基因频率的分布差异均不存在统计学意义(P0.05)。 3、MDD患者性别、婚姻状况、家族史、年龄和首次发病年龄在三种基因型之间的差异均没有统计学意义(P0.05)。 4、携带rs1360780TT基因型患者的第14条目“性症状”分值高于CC基因型和CT基因型患者,差异有统计学意义(P0.05)。不同基因型患者的HAMD总分、迟滞因子、睡眠因子、Maier因子、焦虑／躯体化因子及核心因子分值的差异均无统计学意义(P0.05)。 5、生活事件对MDD的发病有影响(P0.05),FKBP5基因rs1360780位点基因型和二者的交互作用对发病均无影响(P0.05)。结论： 1、FKBP5基因rs1360780位点多态性可能与中国天津地区男性人群MDD发病相关,且携带T等位基因人群患MDD的危险度是携带C等位基因人群的1.608倍,OR(95%CI)为1.608(1.095-2.360)。但是在整体样本人群中或女性人群中均未发现FKBP5基因rs1360780位点多态性与MDD发病存在显著关联。2、FKBP5基因rs1360780位点多态性可能与MDD患者的性别、婚姻状况、家族史、年龄以及首次发病年龄均无显著关联。 3、FKBP5基因rs1360780位点多态性可能与MDD患者迟滞症状中的“性症状”相关,而与MDD患者的抑郁严重程度、迟滞症状、睡眠症状、Maier症状、焦虑/躯体化症状以及核心症状均无显著关联。 4、生活事件对MDD的发病有影响,FKBP5基因rs1360780位点基因型及其与生活事件的交互作用对发病均无影响。
[Abstract]:Objective:The abnormal function of hypothalamus-pituitary-adrenal axis and the continuous increase of glucocorticoid glucocorticoid are considered to be one of the main causes of MDD, and FKBP5 is an important regulator of HPA axis reactivity and GC sensitivity.To explore the relationship between the polymorphism of rs1360780 locus of FKBP5 gene and the pathogenesis of MDD, the relationship between clinical phenotypes and the interaction with life events on the pathogenesis of MDD from the molecular biological level, and to further study the pathogenesis of MDD in order to screen the population at risk.Early diagnosis, early intervention and individualized treatment provide theoretical basis for the development of new antidepressants.Methods:A case-control study was conducted to select 500 patients with MDD and 550 normal controls matched with their sex and age according to the diagnostic criteria of DSM-IV.The severity of MDD was assessed by HAMD-17 and life events were assessed by life events scale (les).Genomic DNA was extracted from peripheral venous whole blood of the subjects. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to type the rs1360780 locus polymorphism in the FKBP5 gene.The difference of P < 0. 05 was statistically significant by using SPSS17.0 statistical software package to analyze the data.Results:1 there were three genotypes of rs1360780 locus of FKBP5 gene.There was no significant difference in the frequency of genotype distribution and expected frequency between the case group and the control group, which was in accordance with Hardy-Weinberg 's law.2. There were significant differences in the distribution of genotype and allele frequency of FKBP5 gene rs1360780 locus between the case group and the control group. The risk of MDD in the population with T allele was 1.608 that of C allele.The distribution of genotype and allele frequency in the whole sample or in the female was not significantly different (P 0.05), and there was no significant difference in the distribution of genotype and allele frequency between I. 608 and 95% CI 1.095 and 2.3600.In the whole sample or in the female, there was no significant difference in the distribution of genotype and allele frequency.3There were no significant differences among the three genotypes in sex, marital status, family history, age and age of first onset of MDD.(4) the score of "sexual symptom" in patients with rs1360780TT genotype was higher than that in patients with CC genotype and CT genotype, and the difference was statistically significant (P 0.05).There was no significant difference in total HAMD score, hysteresis factor, sleep factor Maier factor, anxiety / somatization factor and core factor score between different genotypes (P 0.05).5. Life events had no effect on the onset of MDD. The genotype of rs1360780 locus of FKBP5 gene and the interaction of the two had no effect on the onset of MDD.Conclusion:1the polymorphism of rs1360780 locus of FKBP5 gene may be associated with the incidence of MDD in male population in Tianjin, China, and the risk of MDD in the population with T allele is 1.608 times as high as that in the population with C allele (1.608, 1.095-2.360).However, there was no significant association between the polymorphism of rs1360780 locus of FKBP5 gene and the incidence of MDD. The polymorphism of rs1360780 locus of FKBP5 gene may be associated with sex, marital status and family history of MDD patients.There was no significant correlation between age and age at first onset.3Polymorphism of rs1360780 locus of FKBP5 gene may be associated with "sexual symptoms" in patients with MDD, but not with severity of depression, hysteretic symptoms, sleep symptoms, anxiety / somatization symptoms and core symptoms in MDD patients.4. Life events had no effect on the onset of MDD. The genotype of rs1360780 locus of FKBP5 gene and its interaction with life events had no effect on the onset 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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