抑郁癥快感缺失與DRD3、TREK1基因多態(tài)性的關(guān)聯(lián)研究
發(fā)布時間：2018-07-22 15:45
【摘要】：目的:本研究以具有快感缺失癥狀的抑郁癥患者為研究對象,探討多巴胺D3受體(DRD3)基因多態(tài)性、雙孔鉀通道(TREK1)基因多態(tài)性與抑郁癥快感缺失的相關(guān)性,并進一步探討抑郁癥快感缺失癥狀可能的遺傳學(xué)機制。方法:選取110例符合DSM-5診斷標準,24項漢密爾頓抑郁量表(HAMD)評分≥21分、快感缺失量表(SHAPS表)評定≥3分的抑郁癥患者為病例組,102例心身健康且經(jīng)SHAPS評定3分的健康志愿者為正常對照組。所有研究對象均來自北方漢族人群。所有入組對象均采取血液樣本提取DNA,選擇TREK1的SNPs遺傳標記rs12136349、rs2841608、rs2841616、rs10494996和DRD3的SNP遺傳標記rs6280等位點,分別對各位點進行測序,并進行關(guān)聯(lián)分析。采用SPSS22.0統(tǒng)計學(xué)軟件對數(shù)據(jù)進行處理分析,病例組和對照組各個位點不同基因型及等位基因頻率分布比較采用c2檢驗,各SNPs位點病例組不同基因型快感缺失的嚴重程度即SHAPS評分的比較采用單因素方差分析,不同嚴重程度快感缺失患者各位點基因型及等位基因的分布比較采用c2檢驗,當P0.05時,差異有統(tǒng)計學(xué)意義�？旄腥笔c抑郁情緒之間的關(guān)系,采用雙變量相關(guān)分析,當P0.05時,認為具有相關(guān)性。結(jié)果:1.Hardy-Weinberg平衡檢驗:5個SNPs位點均符合Hardy-Weinberg平衡(P0.05),說明收集的樣本為完全隨機樣本,具有較好的群體代表性。2.SHAPS快感缺失評分與HAMD抑郁評分的相關(guān)性:基線時,即入院3天內(nèi)SHAPS快感缺失評分與HAMD抑郁總評分經(jīng)雙變量相關(guān)分析,結(jié)果顯示,相關(guān)系數(shù)為0.090,P=0.3520.05,兩者不具有相關(guān)性。進一步分析SHAPS與抑郁量表各因子的相關(guān)性,采用多元逐步線性回歸分析,結(jié)果顯示,SHAPS總分與HAMD遲緩因子相關(guān)(r=0.237,P=0.013)。3.病例組與對照組各個位點基因型的分布比較:實驗組與對照組間TREK1基因的4個位點及DRD3基因的rs6280位點各基因型的分布,差異均無統(tǒng)計學(xué)意義(P值均0.05)。4.病例組與對照組各個位點等位基因的分布比較:對病例組與對照組TREK1基因中各個SNPs位點的等位基因分布情況進行比較,結(jié)果提示,僅rs12136349 A等位基因的頻率病例組較正常對照組明顯增高(P=0.033),其余SNPs位點檢驗結(jié)果均顯示P0.05,差異無統(tǒng)計學(xué)意義;DRD3基因rs6280中,2組差異亦無統(tǒng)計學(xué)意義(P=0.226)。5.不同基因型病例組患者快感缺失嚴重程度的比較:TREK1基因rs12136349位點中,AG與GG基因型之間患者的快感缺失程度比較,差異有統(tǒng)計學(xué)意義(P=0.028);rs2841616位點中不同基因型之間患者的快感缺失程度比較,差異有統(tǒng)計學(xué)意義(P=0.027),組內(nèi)兩兩比較后,結(jié)果顯示,GG與AA、AG基因型相比較,差異有統(tǒng)計學(xué)意義(P值分別為0.018、0.012);在TREK1基因rs2841608與DRD3基因的rs6280,不同基因型之間快感缺失SHAPS評分,差異無統(tǒng)計學(xué)意義(P值分別為0.058、0.275)。6.不同嚴重程度快感缺失患者各位點基因型分布比較:高嚴重程度程度與低嚴重程度快感缺失患者各位點基因型分布比較顯示,TREK1基因在rs2841606、rs2841616兩個位點,基因型分布差異有統(tǒng)計學(xué)意義(P值分別為0.005、0.001);TREK1基因rs12136349、rs10494996位點和DRD3基因rs6280基因型分布差異均無統(tǒng)計學(xué)意義(P值均0.05)。7.高嚴重程度與低嚴重程度快感缺失患者各位點等位基因分布比較:TREK1基因在rs2841606、rs2841616兩個位點等位基因分布差異有統(tǒng)計學(xué)意義(P值分別為0.010、0.001);TREK1基因rs12136349、rs10494996位點和DRD3基因rs6280等位基因分布差異均無統(tǒng)計學(xué)意義(P值均0.05)。8.不同性別患者快感缺失程度的比較及不同性別患者各位點基因型和等位基因分布比較:不同性別之間快感缺失程度及TREK1基因的4個位點與DRD3基因rs6280位點各基因型與等位基因分布比較,差異均無統(tǒng)計學(xué)意義(P值均0.05)。結(jié)論:1.TREK1基因rs12136349、rs2841616位點等位基因及基因型分布的差異可能是抑郁癥快感缺失的遺傳學(xué)機制。2.快感缺失嚴重程度與抑郁嚴重程度不相關(guān),快感缺失可能是抑郁癥的獨立癥狀。3.在中國北方漢族人群中,TREK1基因rs12136349位點A等位基因可能與抑郁癥的發(fā)病有關(guān)系,未發(fā)現(xiàn)DRD3 rs6280和TREK1基因中rs2841608、rs2841616、rs10494996位點單核甘酸多態(tài)性與抑郁癥有關(guān)聯(lián)。
[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.
【學(xué)位授予單位】：濟寧醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：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.
【學(xué)位授予單位】：濟寧醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R749.4
【參考文獻】
相關(guān)期刊論文 前2條
1 徐華;葉冬青;李曉莉;張志s，
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