COMT And PPIEL Methylation In Promotor Regions As The Novel Blood Biomarkers For Bipolar Disorder

Objective:Bipolar disorder is a severe mental disease caused by combination effects of environment and genetic factors with high disabling and inheritance risk.There is increased evidence shows that epigenetic abnormality may closely related to the etiology and prognosis in bipolar disorders.The aim of our study is to explore the effects of levels of methylation of COMT and PPIEL promotor(LMCPP)in the pathogenesis of bipolar disorder as well as their predictive effects of mood stabilizers on the treatment of bipolar disorder.So that we can reveal the pathogenesis of bipolar disorder and diagnostic biomarkers.Methods:(1)We used Polymerase Chain Reaction(PCR)and Pyrosequencing to measure PMLCP of 150 bipolar disorder patients(case group)and 152 controls(control group)before treatment.And we analyzed the differences of LMCPP in two groups and their correlation between LMCPP and sex or age.The relationship between the LMCPP and clinical characteristics were also be analyzed.(2)One hundred and thirty-eight patients with bipolar disorder and 80 controls were followed up.Among them,138 patients are treated with monotherapy by using Sodium Valproate Sustained-release Tablets(Depakin),Quetiapine Fumarate(Seroquel)and Lithium Carbonate Sustained-release Tablets.We measured the LMCPP of two groups at the month of 1,3,6,9 and 12 by using PCR and Pyrosequencing after treatment.During the follow-up period,we separated all subjects into three groups(Bipolar?disorder,Bipolar ? disorder and controls)and compared among groups.And we made a comparative analysis on LMCPP of different treatment groups during the follow-up period.(3)We used Kolmogorov-Smirnov to test whether the data was normally distributed.The mean of different groups was assessed using Student's T-test for two groups and one-way ANOVA for multiple groups.The results were expressed as mean ± SD(X±SD);Chi-square test was used for qualitative data.The correlation between two set of data were evaluated using Person's correlation analysis.Multivariate linear regression analysis dependent variable correlation of continuous variables.We set the significance levels at P<0.05.All tests were two-tailed test.Results:(1)The levels of methylation of COMT and PPIEL promotor of case groups is higher than controls before treatment(P<0.05),but there is no significance difference in bipolar ? disorder and bipolar ? disorder(P > 0.05)as well as positive family history and negative family history of patients(P > 0.05).There were also no significant differences between the depressive episode,manic episode and hypomanic episode.(P > 0.05).But patients with bipolar?disorder have a higher rates of positive family history than bipolar?disorder patients(P<0.05).(2)The LMCPP of bipolar ? disorder and bipolar ? disorder are going down gradually after treatment.But it has no significance differences of LMCPP in bipolar? disorder,bipolar ? disorder and controls at the month of 6 and 9(P > 0.05).Patients who were treated with Sodium Valproate Sustained-release Tablets,Quetiapine Fumarate and Lithium Carbonate Sustained-release Tablets have a lower LMCPP than pre-treatment levels,especially at the 6 month(P<0.05).Conclusions(1)Patients with bipolar disorder have high levels of methylation of COMT and PPIEL promotor.And the levels of methylation in the COMT and PPIEL promoter were consistent among bipolar disorder patients with different clinical characteristics.(2)The levels of methylation of COMT and PPIEL promotor(LMCPP)going down gradually after treatments by using Sodium Valproate Sustained-release Tablets,Quetiapine Fumarate and Lithium Carbonate Sustained-release Tablets(3)The levels of methylation of COMT and PPIEL promotor(LMCPP)can be used as diagnostic biomarker of bipolar disorder.