【作者】 赵国庆；

【导师】 焦志安；

【作者基本信息】 山东大学 ， 精神病与精神卫生学， 2008， 硕士

【摘要】 目的1.检测重性抑郁障碍(Major Depressive Disorder,MDD)患者血浆同型半胱氨酸(Homocysteine,Hcy)水平。2.研究5,10-亚甲基四氢叶酸还原酶(Methylene tetrahydrofolate reductase,MTHFR)基因C677T多态性对血浆同型半胱氨酸水平的影响。3.探讨MTHFR基因C677T多态性与MDD发病的相关性。方法1.采用单纯随机抽样的方法,抽取在山东省精神卫生中心接受住院治疗的77例MDD患者作为研究对象,纳入研究组。另外,随机抽取同时期在某综合医院体检中心进行查体的85名健康者作为正常对照,纳入对照组。2.应用自编一般情况问卷,收集研究组与对照组的一般资料。治疗前对研究组进行汉密尔顿抑郁量表(Hamilton Rating Scale for Depression,HAMD)和汉密尔顿焦虑量表(Hamilton Anxiety Scale,HAMA)评定。3.采用荧光偏振免疫法(Fluorescence Polarization Immunoassay,FPIA)测定血浆Hcy浓度。运用聚合酶链反应-限制性内切酶片段长度多态性分析技术(Polymerase Chain Reaction-Restriction Fragment Length Polymorphism,PCR-RFLP)检测MTHFR基因C677T多态性。结果1.血浆Hcy浓度比较研究组血浆Hcy水平明显高于对照组,差异有统计学意义(t=5.857,P＜0.001)。研究组血浆高Hcy发生率较对照组高,差异有统计学意义(x~2=15.602,P＜0.001)。进一步分层分析,研究组和对照组男、女血浆Hcy浓度分别为(17.69±5.49)μmoL/L、(18.74±5.09)μmoL/L和(14.11±4.82)μmoL╱L、(13.38±5.12)μmoL╱L,组内男、女Hcy浓度差异均无统计学意义(t=0.845,P＞0.05;t=0.646,P＞0.05);复发患者Hcy浓度明显高于首发患者[(19.69±4.91)μmoL/L vs.(16.04±5.04)μmoL/L,t=3.110,P＜0.05];MDD家族史阳性患者Hcy浓度高于家族史阴性患者[(21.02±5.29)μmoL/L vs.(16.92±4.65)μmoL/L,t=3.518,P＜0.001]。研究组各基因型血浆Hcy浓度均高于对照组相应基因型,差异有统计学意义(P＜0.05)。研究组和对照组内TT型Hcy浓度均较CT型、CC型高,差异有统计学意义(P＜0.05)。2.MTHFR基因多态性比较经x~2吻合度检验,研究组和对照组基因型分布均符合Hardy-Weinberg平衡定律(P＞0.05),所选样本具有群体代表性。研究组与对照组基因型频率比较,差异有统计学意义(x~2=6.772,P=0.034)。研究组T等位基因频率明显高于对照组(x~2=4.287,P=0.038)。TT型与非TT型患病风险比值(Odd Ratio,OR)为2.464,95%可信区间为(Confidence Interval,CI):1.205～5.038。研究组内男、女之间MTHFR基因型频率比较差异有统计学意义(x~2=7.404,P=0.025);首发与复发患者MTHFR基因型频率比较差异均无统计学意义(x~2=3.078,P=0.215);MDD家族史阳性与阴性患者MTHFR基因型频率比较差异亦无统计学意义(x~2=0.664,P=0.717)。3.HAMD评分比较MTHFR各基因型间HAMD评分差异有统计学意义(F=18.958,P=0.000)。两两比较,TT型HAMD评分明显高于CT型和CC型,差异有统计学意义(P＜0.05);CT型与CC型HAMD评分比较差异无统计学意义(P=0.251)。经Pearson相关分析,Hcy浓度与HAMD评分呈明显正相关,(r=0.473,P=0.000)。4.HAMA评分比较MTHFR各基因型间HAMA评分差异无统计学意义(F=0.257,P=0.774)。进一步两两比较,TT型HAMA评分与CT型和CC型,等异均无统计学意义(P＞0.05);CT型与CC型HAMA评分差异亦无统计学意义(P＞0.05)。经Pearson相关分析,Hcy浓度与HAMA评分相关性不明显,(r=0.112,P=0.333)。5.MDD患者Hcy水平的影响因素经多元逐步回归分析,MDD患者血浆Hcy水平与年龄、家族史、携带TT基因型及MDD发作次数有关(R~2=0.585,F=20.010,P=0.000)。结论1.血浆Hcy浓度升高可能是MDD的一个危险因素,血浆Hcy浓度越高可能预示患者MDD的病情越严重。2.血浆Hcy浓度的相关因素有年龄、MDD家族史、发作次数及携带TT基因型。3.MTHFR基因C677T多态性可能是MDD的遗传易感因素,其可能通过影响血浆Hcy水平而参与了MDD的发病及临床表现。更多还原

【Abstract】 [OBJECTIVE]1.To investigate the difference of plasma levels of homocysteine(Hcy)between patients of major depressive disorder(MDD)and normal controls.2.To study the influence of polymorphisms of 5,10-methylene tetrahydrofolate reductase(MTHFR)on the plasma Hey levels.3.To explore the relationships of polymorphisms of MTHFR gene C677T and MDD.[METHODS]1.A total of 77 MDD cases were sampled from hospitalized patients of Shandong Mental Health Center.Moreover,a total of 85 healthy controls were taken from medical examination center of a certain general hospital.2.Basic information questionnaire was administrated to all subjects.Hamilton Rating Scale for Depression(HAMD,17-item)and Hamilton Anxiety Scale (HAMA)were examed at the baseline in the study group.3.The plasma Hey levels were determined by fluorescence polarization immunoassay(FPIA).And,the genotypes of MTHFR C677T were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR -RFLP)in two groups. [RESULTS]1.To compare the plasma Hcy levelsThe plasma levels of Hcy in the study group were significantly higher than those in the control group.There was a higher incidence of hyperhomocysteinemia(HHcy) in study group than in control group.No difference of Hey levels was investigated between male and female in both study group and control group.Relapse patients had higer Hey levels than the first attack patients and the patients with positive family history had significantly higher Hey levels than those with nagitive family history.Hey levels of any genotypes in study group are higher than that of corresponding genotypes in control group.Plasma Hey levels of TT genotype in patients and controls were obviously higher than those of CT and CC genotype.2.The polymorphisms of MTHFR gene C677TThe distributions of MTHFR gene C677T polymorphism in study group and control group were all in accordance with the law of Hardy-Weinberg equilibrium (P＞0.05).There were significant differences in genotype frequencies and allele frequencies between study and control group(P＜0.05).T allele frequency in study group was higher than that in control group.For MDD,the odds ratio for TT versus non-TT genotype was 2.464,95%CI: 1.205～5.038.The distributions of MTHFR genotypes were associated with gender(P＜0.05) but no association was found with frequency of MDD attacks and family medical history.(P＞0.05)。3.The score of HAMDThe total scores of HAMD in different genotypes of MTHFR had significant differences(F=18.958,P=0.000)。Compared to CT and CC,TT genotype had higher HAMD scores(P＜0.05);There was no significant difference of HAMD scores between CT and CC(P＞0.05)。 The total scores of HAMD were positively relevant to plasma Hey levels(r= 0.473,P=0.002)。4.The score of HAMAThe total scores of HAMA in different genotypes of MTHFR had no significant differences(F=0.257,P=0.774)。There was no significant difference of HAMA scores among TT、CT and CC(P＞0.05)。The total scores of HAMA were not relevant to plasma Hey levels(r=0.112, P=0.333)。5.The main influencing factors of Hcy in MDD patientsBy adopting multiple stepwise regression analysis,the plasma Hcy levels were significantly correlated with age、TT genotype、frequency of MDD attacks and family medical history。[CONCLUSION]1.Elevation in plasma Hcy levels should be a risk factor of major depressive disorder.Plasma Hcy levels may be used to predict the severity of MDD.2.The related factors of Hcy include:age、frequency of MDD attacks、family medical history and polymorphisms of MTHFR C677T.3.The polymorphisms of MTHFR C677T may be hereditary predisposing factor of MDD,which may be included in the onset and clinical situation of MDD by influencing levels of Hcy.更多还原