The Possible Role Of Differentially Methylated Gene Expression In The Pathogenesis Of Tardive Dyskinesia

Objective: To investigate the possible role of abnormally methylate in the pathogenesis of tardive dyskinesia(TD)by analyzing the difference of the expression level of differentially methylated genes in schizophrenia and schizophrenia with TD,so as to provide theoretical basis for early clinical diagnosis,prevention and specific targeted therapy.Methods: fifty-six schizophrenia patients meeting DSM-IV criteria with TD(TD group,n=28),without TD(NTD group,n=28),normal group(HC group,n=28)were selected.The positive and negative symptom scale(PANSS)and AIMS scale were used to assess the severity of TD.The mRNA expression levels of CYP2E1 gene,C4A/B gene,DLGAP2 gene,GSTA4 gene,MPC gene,PLCXD1 gene and PSMB5 gene were detected by Real-time fluorescence quantification PCR.Results:(1)The expression levels of CYP2E1 gene [(3.52±4.34)vs.(1.10±1.14)].MPC gene [(1.46±1.16)vs.(1.08±0.73)] and PLCXD1 gene [(1.08±2.01)vs.(1.53±1.50] was higher in the schizophrenia group than in HC group.(2)There were significant differences in the expression levels of CYP2E1 gene(H = 10.47,P = 0.005),C4A/B gene(H = 7.26,P = 0.027),MPC gene(H = 6.57,P = 0.037),PLCXD1 gene(H = 6.77,P = 0.034)different among the three groups of TD,NTD and HC.It was found that the expression of CYP2E1 gene in TD group was higher than that in NTD group [(4.70±5.05)vs.(2.34±3.17),P=0.005].(3)The analyses was show that the expression level of DLGAP2 gene was positively correlated with the age of morbidity(r=0.38,P=0.046),while the expression level of MPC gene was negatively correlated with the total score of AIMS(r=-0.54,P=0.004).(4)The expression of MPC gene [(1.69±1.34)vs.(0.90±0.36]and PSMB5 gene [(1.31±0.56)vs.(0.86±0.27]in TD group was higher than that in TD group.Conclusions:(1)In patients with TD,the increased expression of CYP2E1 may be involved in the pathogenesis of TD through oxidative stress due to the decreased methylation level of CYP2E1 gene.(2)The differential expression of MPC gene in patients with TD,especially in men,suggests that it may play a role in the pathogenesis of TD.(3)The expression of differentially expressed genes C4A/B and DLGAP2 regulated by DNA methylation may be related to the pathogenesis of schizophrenia.