抑郁症快感缺失与DRD3、TREK1基因多态性的关联研究
发布时间：2018-07-22 15:45
【摘要】：目的:本研究以具有快感缺失症状的抑郁症患者为研究对象,探讨多巴胺D3受体(DRD3)基因多态性、双孔钾通道(TREK1)基因多态性与抑郁症快感缺失的相关性,并进一步探讨抑郁症快感缺失症状可能的遗传学机制。方法:选取110例符合DSM-5诊断标准,24项汉密尔顿抑郁量表(HAMD)评分≥21分、快感缺失量表(SHAPS表)评定≥3分的抑郁症患者为病例组,102例心身健康且经SHAPS评定3分的健康志愿者为正常对照组。所有研究对象均来自北方汉族人群。所有入组对象均采取血液样本提取DNA,选择TREK1的SNPs遗传标记rs12136349、rs2841608、rs2841616、rs10494996和DRD3的SNP遗传标记rs6280等位点,分别对各位点进行测序,并进行关联分析。采用SPSS22.0统计学软件对数据进行处理分析,病例组和对照组各个位点不同基因型及等位基因频率分布比较采用c2检验,各SNPs位点病例组不同基因型快感缺失的严重程度即SHAPS评分的比较采用单因素方差分析,不同严重程度快感缺失患者各位点基因型及等位基因的分布比较采用c2检验,当P0.05时,差异有统计学意义。快感缺失与抑郁情绪之间的关系,采用双变量相关分析,当P0.05时,认为具有相关性。结果:1.Hardy-Weinberg平衡检验:5个SNPs位点均符合Hardy-Weinberg平衡(P0.05),说明收集的样本为完全随机样本,具有较好的群体代表性。2.SHAPS快感缺失评分与HAMD抑郁评分的相关性:基线时,即入院3天内SHAPS快感缺失评分与HAMD抑郁总评分经双变量相关分析,结果显示,相关系数为0.090,P=0.3520.05,两者不具有相关性。进一步分析SHAPS与抑郁量表各因子的相关性,采用多元逐步线性回归分析,结果显示,SHAPS总分与HAMD迟缓因子相关(r=0.237,P=0.013)。3.病例组与对照组各个位点基因型的分布比较:实验组与对照组间TREK1基因的4个位点及DRD3基因的rs6280位点各基因型的分布,差异均无统计学意义(P值均0.05)。4.病例组与对照组各个位点等位基因的分布比较:对病例组与对照组TREK1基因中各个SNPs位点的等位基因分布情况进行比较,结果提示,仅rs12136349 A等位基因的频率病例组较正常对照组明显增高(P=0.033),其余SNPs位点检验结果均显示P0.05,差异无统计学意义;DRD3基因rs6280中,2组差异亦无统计学意义(P=0.226)。5.不同基因型病例组患者快感缺失严重程度的比较:TREK1基因rs12136349位点中,AG与GG基因型之间患者的快感缺失程度比较,差异有统计学意义(P=0.028);rs2841616位点中不同基因型之间患者的快感缺失程度比较,差异有统计学意义(P=0.027),组内两两比较后,结果显示,GG与AA、AG基因型相比较,差异有统计学意义(P值分别为0.018、0.012);在TREK1基因rs2841608与DRD3基因的rs6280,不同基因型之间快感缺失SHAPS评分,差异无统计学意义(P值分别为0.058、0.275)。6.不同严重程度快感缺失患者各位点基因型分布比较:高严重程度程度与低严重程度快感缺失患者各位点基因型分布比较显示,TREK1基因在rs2841606、rs2841616两个位点,基因型分布差异有统计学意义(P值分别为0.005、0.001);TREK1基因rs12136349、rs10494996位点和DRD3基因rs6280基因型分布差异均无统计学意义(P值均0.05)。7.高严重程度与低严重程度快感缺失患者各位点等位基因分布比较:TREK1基因在rs2841606、rs2841616两个位点等位基因分布差异有统计学意义(P值分别为0.010、0.001);TREK1基因rs12136349、rs10494996位点和DRD3基因rs6280等位基因分布差异均无统计学意义(P值均0.05)。8.不同性别患者快感缺失程度的比较及不同性别患者各位点基因型和等位基因分布比较:不同性别之间快感缺失程度及TREK1基因的4个位点与DRD3基因rs6280位点各基因型与等位基因分布比较,差异均无统计学意义(P值均0.05)。结论:1.TREK1基因rs12136349、rs2841616位点等位基因及基因型分布的差异可能是抑郁症快感缺失的遗传学机制。2.快感缺失严重程度与抑郁严重程度不相关,快感缺失可能是抑郁症的独立症状。3.在中国北方汉族人群中,TREK1基因rs12136349位点A等位基因可能与抑郁症的发病有关系,未发现DRD3 rs6280和TREK1基因中rs2841608、rs2841616、rs10494996位点单核甘酸多态性与抑郁症有关联。
[Abstract]:Objective: To explore the correlation between the polymorphism of dopamine D3 receptor (DRD3) gene, the polymorphism of the double pore potassium channel (TREK1) gene and the deletions of depression, and further explore the possible genetic mechanism of the depressive disorder. Methods: 110 cases were selected to meet the DSM-5 diagnosis. The 24 Hamilton Depression Scale (HAMD) score was more than 21, and the Depression Scale (SHAPS) for the depression was more than 3 in the case group. 102 healthy volunteers with mental health and 3 points of SHAPS were used as the normal control group. All the subjects were from the northern Han population. All the subjects were collected from the blood samples. DNA, select the SNPs genetic markers of TREK1, rs2841608, rs2841616, rs10494996, and DRD3 of SNP genetic markers, rs6280 and other loci, to sequence and analyze each point respectively. The data are processed and analyzed by SPSS22.0 statistics software. The frequency of different genotypes and alleles at each site of the case group and the irradiated group is divided. C2 test was used. The severity of different genotype express deletion in the SNPs loci group was compared with the single factor variance analysis. The distribution of genotypes and alleles of each point in patients with different severity of express deletion were compared with C2 test. When P0.05, the difference was statistically significant. The loss of pleasure and depression were significant. The relationship between the threads, using bivariate correlation analysis, was considered to be relevant when P0.05. Results: 1.Hardy-Weinberg balance test: 5 SNPs loci were all conformed to Hardy-Weinberg balance (P0.05), indicating that the collected samples were complete random samples, and there was a good correlation between the group representative.2.SHAPS pleasure loss score and the HAMD depression score. At baseline, SHAPS loss score and HAMD depression score were analyzed by bivariate correlation in 3 days of admission. The results showed that the correlation coefficient was 0.090, P=0.3520.05, and there was no correlation between them. Further analysis of the correlation between the factors of SHAPS and the depression scale was further analyzed by multiple stepwise linear regression analysis. The results showed that the total score of SHAPS and the delay of HAMD were slow. Factor related (r=0.237, P=0.013).3. case group and the control group the distribution of loci genotypes: the 4 loci of the TREK1 gene between the experimental group and the control group and the distribution of the rs6280 loci of the DRD3 gene, the difference was not statistically significant (P value was 0.05) the distribution of the alleles of each loci in the.4. case group and the control group: to the disease. The distribution of alleles of all SNPs loci in the TREK1 gene of the control group was compared. The results showed that the frequency case group of only the rs12136349 A allele was significantly higher than that of the normal control group (P=0.033), and the other SNPs locus test results showed P0.05, and the difference was not statistically significant, and there was no statistical difference between the 2 groups of DRD3 gene rs6280. A comparison of the severity of the loss of pleasure in patients with different genotype cases (P=0.226).5.: in the TREK1 gene rs12136349 locus, the difference in the degree of pleasure loss between the AG and the GG genotypes was statistically significant (P=0.028), and the difference in the degree of pleasure loss between the patients with different genotypes in the rs2841616 site was statistically significant. P=0.027, after 22 comparison, the results showed that the difference between GG and AA and AG genotype was statistically significant (P value was 0.018,0.012), and the SHAPS score between the TREK1 gene rs2841608 and rs6280 of the DRD3 gene was between the different genotypes, and the difference was not significant (P values were respectively). Comparison of genotypic distribution of all points in the patients: the distribution of genotype distribution in patients with high severity and low severity loss showed that the TREK1 gene was at two sites in rs2841606 and rs2841616, and the difference in genotype distribution was statistically significant (P value was 0.005,0.001), TREK1 gene rs12136349, rs10494996 site and DRD3 RS. The distribution of 6280 genotypes was not statistically significant (P value 0.05).7. high severity and low severity loss of the allele distribution: TREK1 gene in rs2841606, rs2841616 two loci allele distribution difference was statistically significant (P value is 0.010,0.001, respectively); TREK1 gene rs12136349, rs10494996 locus. There was no statistical difference between the allele distribution of rs6280 and DRD3 gene (P value 0.05) the comparison of the degree of express deletion in different sex patients with.8. and the distribution of genotypes and alleles in different sex patients: the degree of express deletion between different sexes, the 4 loci of TREK1 gene and the genotype and and so on of the rs6280 locus of the DRD3 gene. There was no significant difference in the distribution of alleles (P value 0.05). Conclusion: the difference in the 1.TREK1 gene rs12136349, rs2841616 allele and genotype distribution may be the genetic mechanism of the deletions of depression, the severity of.2. loss is not related to the severity of depression, and the loss of pleasure may be an independent symptom of depression. .3. in the Han population of northern China, the A allele of the rs12136349 locus of the TREK1 gene may be associated with the onset of depression. No rs2841608, rs2841616, and rs10494996 loci of the DRD3 rs6280 and TREK1 genes are found to be associated with depression.
【学位授予单位】：济宁医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.4
[Abstract]:Objective: To explore the correlation between the polymorphism of dopamine D3 receptor (DRD3) gene, the polymorphism of the double pore potassium channel (TREK1) gene and the deletions of depression, and further explore the possible genetic mechanism of the depressive disorder. Methods: 110 cases were selected to meet the DSM-5 diagnosis. The 24 Hamilton Depression Scale (HAMD) score was more than 21, and the Depression Scale (SHAPS) for the depression was more than 3 in the case group. 102 healthy volunteers with mental health and 3 points of SHAPS were used as the normal control group. All the subjects were from the northern Han population. All the subjects were collected from the blood samples. DNA, select the SNPs genetic markers of TREK1, rs2841608, rs2841616, rs10494996, and DRD3 of SNP genetic markers, rs6280 and other loci, to sequence and analyze each point respectively. The data are processed and analyzed by SPSS22.0 statistics software. The frequency of different genotypes and alleles at each site of the case group and the irradiated group is divided. C2 test was used. The severity of different genotype express deletion in the SNPs loci group was compared with the single factor variance analysis. The distribution of genotypes and alleles of each point in patients with different severity of express deletion were compared with C2 test. When P0.05, the difference was statistically significant. The loss of pleasure and depression were significant. The relationship between the threads, using bivariate correlation analysis, was considered to be relevant when P0.05. Results: 1.Hardy-Weinberg balance test: 5 SNPs loci were all conformed to Hardy-Weinberg balance (P0.05), indicating that the collected samples were complete random samples, and there was a good correlation between the group representative.2.SHAPS pleasure loss score and the HAMD depression score. At baseline, SHAPS loss score and HAMD depression score were analyzed by bivariate correlation in 3 days of admission. The results showed that the correlation coefficient was 0.090, P=0.3520.05, and there was no correlation between them. Further analysis of the correlation between the factors of SHAPS and the depression scale was further analyzed by multiple stepwise linear regression analysis. The results showed that the total score of SHAPS and the delay of HAMD were slow. Factor related (r=0.237, P=0.013).3. case group and the control group the distribution of loci genotypes: the 4 loci of the TREK1 gene between the experimental group and the control group and the distribution of the rs6280 loci of the DRD3 gene, the difference was not statistically significant (P value was 0.05) the distribution of the alleles of each loci in the.4. case group and the control group: to the disease. The distribution of alleles of all SNPs loci in the TREK1 gene of the control group was compared. The results showed that the frequency case group of only the rs12136349 A allele was significantly higher than that of the normal control group (P=0.033), and the other SNPs locus test results showed P0.05, and the difference was not statistically significant, and there was no statistical difference between the 2 groups of DRD3 gene rs6280. A comparison of the severity of the loss of pleasure in patients with different genotype cases (P=0.226).5.: in the TREK1 gene rs12136349 locus, the difference in the degree of pleasure loss between the AG and the GG genotypes was statistically significant (P=0.028), and the difference in the degree of pleasure loss between the patients with different genotypes in the rs2841616 site was statistically significant. P=0.027, after 22 comparison, the results showed that the difference between GG and AA and AG genotype was statistically significant (P value was 0.018,0.012), and the SHAPS score between the TREK1 gene rs2841608 and rs6280 of the DRD3 gene was between the different genotypes, and the difference was not significant (P values were respectively). Comparison of genotypic distribution of all points in the patients: the distribution of genotype distribution in patients with high severity and low severity loss showed that the TREK1 gene was at two sites in rs2841606 and rs2841616, and the difference in genotype distribution was statistically significant (P value was 0.005,0.001), TREK1 gene rs12136349, rs10494996 site and DRD3 RS. The distribution of 6280 genotypes was not statistically significant (P value 0.05).7. high severity and low severity loss of the allele distribution: TREK1 gene in rs2841606, rs2841616 two loci allele distribution difference was statistically significant (P value is 0.010,0.001, respectively); TREK1 gene rs12136349, rs10494996 locus. There was no statistical difference between the allele distribution of rs6280 and DRD3 gene (P value 0.05) the comparison of the degree of express deletion in different sex patients with.8. and the distribution of genotypes and alleles in different sex patients: the degree of express deletion between different sexes, the 4 loci of TREK1 gene and the genotype and and so on of the rs6280 locus of the DRD3 gene. There was no significant difference in the distribution of alleles (P value 0.05). Conclusion: the difference in the 1.TREK1 gene rs12136349, rs2841616 allele and genotype distribution may be the genetic mechanism of the deletions of depression, the severity of.2. loss is not related to the severity of depression, and the loss of pleasure may be an independent symptom of depression. .3. in the Han population of northern China, the A allele of the rs12136349 locus of the TREK1 gene may be associated with the onset of depression. No rs2841608, rs2841616, and rs10494996 loci of the DRD3 rs6280 and TREK1 genes are found to be associated with depression.
【学位授予单位】：济宁医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.4
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1 徐华;叶冬青;李晓莉;张志s，
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