本文選題：重性抑郁障礙　切入點(diǎn)：FKBP5　出處：《天津醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的： 下丘腦-垂體-腎上腺軸(HPA軸)功能異常以及糖皮質(zhì)激素(GC)持續(xù)升高被認(rèn)為是引起重性抑郁障礙(MDD)的主要原因之一,且FKBP5為HPA軸反應(yīng)性以及GC敏感性的重要調(diào)整者。從分子生物學(xué)水平探索FKBP5基因rs1360780位點(diǎn)多態(tài)性與MDD的發(fā)病、臨床表型之間的關(guān)系以及與生活事件的交互作用對MDD發(fā)病的影響,進(jìn)一步研究MDD的發(fā)病機(jī)制,為篩選危險(xiǎn)人群、早期診斷、早期干預(yù)及個(gè)體化治療提供理論依據(jù),為新型抗抑郁藥物的研發(fā)提供新思路。方法： 采用病例-對照研究方法,嚴(yán)格按照DSM-IV診斷標(biāo)準(zhǔn),選取500例MDD患者和550例與之性別、年齡相匹配的正常對照作為研究對象。采用HAMD-17評定MDD的嚴(yán)重程度,同時(shí)采用生活事件量表(LES)對病例組和對照組的生活事件進(jìn)行評定。抽取被試外周靜脈全血,提取基因組DNA,采用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性(PCR-RFLP)方法對FKBP5基因上的rs1360780位點(diǎn)多態(tài)性進(jìn)行分型。運(yùn)用SPSS17.0統(tǒng)計(jì)軟件包進(jìn)行數(shù)據(jù)分析,P小于0.05為差異有統(tǒng)計(jì)學(xué)意義。 結(jié)果： 1、FKBP5基因rs1360780位點(diǎn)有三種基因型CC、CT和TT。病例組和對照組中各基因型分布頻率與期望頻率的差別沒有統(tǒng)計(jì)學(xué)差異,符合Hardy-Weinberg定律。 2、病例組和對照組FKBP5基因rs1360780位點(diǎn)各基因型和等位基因頻率的分布差異在男性中均有統(tǒng)計(jì)學(xué)意義(P0.05),并且攜帶T等位基因的人群患MDD的危險(xiǎn)度是攜帶C等位基因的1.608倍(OR=I.608,95%CI1.095～2.360)；而在整體樣本中或女性中各基因型及等位基因頻率的分布差異均不存在統(tǒng)計(jì)學(xué)意義(P0.05)。 3、MDD患者性別、婚姻狀況、家族史、年齡和首次發(fā)病年齡在三種基因型之間的差異均沒有統(tǒng)計(jì)學(xué)意義(P0.05)。 4、攜帶rs1360780TT基因型患者的第14條目“性癥狀”分值高于CC基因型和CT基因型患者,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。不同基因型患者的HAMD總分、遲滯因子、睡眠因子、Maier因子、焦慮／軀體化因子及核心因子分值的差異均無統(tǒng)計(jì)學(xué)意義(P0.05)。 5、生活事件對MDD的發(fā)病有影響(P0.05),FKBP5基因rs1360780位點(diǎn)基因型和二者的交互作用對發(fā)病均無影響(P0.05)。 結(jié)論： 1、FKBP5基因rs1360780位點(diǎn)多態(tài)性可能與中國天津地區(qū)男性人群MDD發(fā)病相關(guān),且攜帶T等位基因人群患MDD的危險(xiǎn)度是攜帶C等位基因人群的1.608倍,OR(95%CI)為1.608(1.095-2.360)。但是在整體樣本人群中或女性人群中均未發(fā)現(xiàn)FKBP5基因rs1360780位點(diǎn)多態(tài)性與MDD發(fā)病存在顯著關(guān)聯(lián)。2、FKBP5基因rs1360780位點(diǎn)多態(tài)性可能與MDD患者的性別、婚姻狀況、家族史、年齡以及首次發(fā)病年齡均無顯著關(guān)聯(lián)。 3、FKBP5基因rs1360780位點(diǎn)多態(tài)性可能與MDD患者遲滯癥狀中的“性癥狀”相關(guān),而與MDD患者的抑郁嚴(yán)重程度、遲滯癥狀、睡眠癥狀、Maier癥狀、焦慮/軀體化癥狀以及核心癥狀均無顯著關(guān)聯(lián)。 4、生活事件對MDD的發(fā)病有影響,FKBP5基因rs1360780位點(diǎn)基因型及其與生活事件的交互作用對發(fā)病均無影響。
[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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R749.4

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相關(guān)期刊論文 前1條

1 伊茂森,翟昕東,李文紅;精神障礙的性別差異[J];國外醫(yī)學(xué)(精神病學(xué)分冊);2002年04期

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本文編號：1704621