ABSTRACT
Objective To investigate the effects of stress on the methylation of brain derived neurotrophic factor gene in the patients with major depressive disorder (MDD),and to investigate the relationship between BDNF gene methylation and MDD.Methods 47 cases of MDD were divided into MDD stress group (n=24) and MDD non stress group(n=23) while 27 health subjects were collected as normal control group.The methylation status of CpG island in the promoter region of BDNF gene in peripheral blood was detected by the method of heavy hydrogen and hydrogen sulfate.SPSS17.0 statistical software package was used to analyze the data.The differences of 19 CpG methylation rates and the overall level of methylation rates of three groups were analyzed.Results The CpG overall methylation rates (median,interquartile range) of MDD stress group,MDD non stress group and normal control group was 189.150 (7.575),188.500 (400)and 480.200(770) respectively,and the difference was statistically significant (P＜0.01).There was no significant difference in the overall methylation rate of CpG in the MDD stress group compared with MDD non stress group (P＞0.05).The CpG methylation rates (mean± SD or median,interquartile range) of three groups were detected as follows:CpG-1:2.600(0.275),2.700 (0.400),6.500(0.800);CpG-2:3.350(0.650),3.300(0.800),14.600(1.500);CpG-3:1.596±0.363,1.543±0.400,4.581 ±0.437;CpG-4:1.779±0.516,1.522±0.329,4.033 ±0.529;CpG-5:0.900 (0.575),0.800 (0.600),5.700 (1.500);CpG-6:6.258 ± 0.805,6.213 ±0.944,14.589±0.819;CpG-7:10.667±0.894,10.283± 1.006,15.000±0.763;CpG-8:16.421 ±0.697,16.330±0.775,24.796±0.547;CpG-9:4.713±0.565,4.891 ±0.554,28.826±0.679;CpG-10:10.254±0.902,10.378±0.777,11.381±0.538;CpG-11:24.125±2.301,24.170±2.613,37.474± 1.579;CpG-12:5.442±0.641,5.596±1.117,12.141 ±0.940;CpG-13:4.150(1.150),4.200(1.000),61.700(4.800);CpG-14:5.500±0.544,5.717±0.568,6.378±0.397;CpG-15:3.700 (0.700),4.100(1.000),63.300(2.500);CpG-16:8.200 (1.775),8.100(1.500),75.200(3.300);CpG-17:3.250(0.550),3.300(0.800),34.600(5.000);CpG-18:1.988±0.279,1.939±0.259,2.330±0.207;CpG-19:35.338±2.421,35.187±2.259,65.941 ±2.692.16 CpG methylation rates of 19 CpG were higher in MDD stress group and MDD non stress group.Compared with the normal control group,the difference was statistically significant (P＜0.01).There was no significant difference in CpG methylation rate between MDD stress group and MDD non stress group (P＞0.05).Conclusion The overall methylation rate of CpG in BDNF gene promoter region is closely related with MDD,which may affect the incidence of MDD.There was no correlation between CpG methylation in BDNF gene promoter region and MDD,and stressful life events may not be the direct cause of CpG methylation in BDNF gene promoter region in patients with MDD.
ABSTRACT
Objective To explore the role of brain derived neurotrophic factor(BDNF) promoter methylation for the morbidity of depression patients,and to investigate the relevance between BDNF promoter methylation and the suicidal ideation in patients with first-episode major depressive disorder.Methods The peripheral blood samples from 23 cases of depression patients with suicide ideation ,24 cases of depression patients without suicide ideation,and 27 healthy controls were grouped using simple randomization method, and the methylation status of CpG island of BDNF promoter were subsequently evaluated using bisulphite sequencing.Results The methylation rates(median,quartile interval) of depression patients with suicidal ideation, depression patients without suicidal attempt, and the healthy control were detected as follows, CPG-1 : 2.60 (0.28), 2.70 (0.60), 6.40 (1.00);CPG-2:3.35 (1.15),3.20 (1.00),14.50 (2.60);CPG-3:1.50 (0.40),1.50 (0.60),4.60 (0.90);CPG-4:1.75 (0.90) ,1.50 (0.50),3.90 (0.90);CPG-5:0.80 (0.58),0.90 (1.00),5.70 (2.10);CPG-6:6.05 (1.03),6.20 (1.70), 14.50 (1.70);CPG-7:10.55 (1.68), 10.10 (1.50), 14.70 (1.70);CPG-8:16.35 (0.90), 16.40 (1.00),4.80 (1.20);CPG-9:4.20 (4.80),4.70 (1.30),28.50 (19.30);CPG-10:10.25 (1.08),10.30 (1.20) ,4.30 (0.90);CPG-11:62.80 (4.05) ,62.30 (4.00) ,37.20 (2.60);CPG-12:5.60 (1.05) ,5.60 (1.30) ,12.30 (1.80);CPG-13:4.15 (1.10) ,4.10 (1.10) ,59.70 (4.90);CPG-14:5.45 (0.78) ,5.70 (0.90),6.30 (0.60);CPG-15:3.70 (0.70) ,3.90 (1.00) ,62.40 (6.50);CPG-16:8.05 (1.75) ,8.10 (1.60) ,74.30 (50.90);CPG-17:3.20 (0.78),3.20 (0.80),32.40 (13.20);CPG-18:1.90 (0.48),1.80 (0.40),2.30 (0.30);CPG-19 : 35.00 (6.27), 35.20 (3.00), 64.20 (44.70).There was an obvious difference in methylation rate among three groups,which was statistically significant (P＜0.01).However, no statistical significance for the methylation rates was observed between the depression patients with suicidal ideation and without suicidal ideation.Interestingly, statistical significance for the methylation rates were observed when compared the depression patients with suicidal ideation with healthy control (P＜ 0.05), and the depression patients without suicidal ideation with healthy control (P＜0.05).Conclusion The results show that the association is observed between BDNF promoter methylation and the morbidity of depressive disorder,but not between BDNF promoter methylation and the suicidal ideation of depression patients.