| Objective(s): To investigate the correlation between the levels of DNA methylation in the promoter regions of MAOA and COMT genes in peripheral venous blood and the gender difference in schizophrenia,so as to provide reference for the occurrence and development of schizophrenia in epigenetics.Methods:According to the inclusion and exclusion criteria,the study population was screened and 5ml peripheral venous blood was collected from healthy control group and schizophrenia group.DNA was extracted by the QIAamp DNA Blood Mini Kit and the samples were treated with bisulfite conversion.The methylation status of Cp G sites in and around the target fragments in the promoter regions of MAOA and COMT genes was detected by Methyl Target technology.SPSS 22.0 software was used for statistical analysis of the data,and Graph Pad Prism 9 software was used to draw the statistical diagram.Results:1.General characteristics of the research object There are 86 cases in the control group(64 males and 22 females)and 80 cases in the schizophrenia group(56 males and 24 females),all of whom are Han nationality.Their ages were 39.18±10.61 and 42.99±10.46 years old,and their body mass index(BMI)were 21.99±4.81 and 22.27±3.33,respectively.After sex stratification,the ages of male control group and case group were 37.96±10.87 and44.01±11.65 years old respectively,and BMI values were 21.19±4.63 and 22.14±3.30 respectively.The age of the control group and the case group were 40.33±6.38 and40.63±6.58 years old,and the BMI values were 21.19±4.63 and 22.14±3.30 respectively.There was no significant difference in age and BMI between groups(P >0.05).2.Correlation between methylation level of MAOA gene fragment and SCZ Two target fragments,MAOA＿1 and MAOA＿2,were detected in the promoter region of MAOA gene. The MAOA＿1 fragment was located in the Chr X:43514479-43514728 region,325 bp from the transcription initiation site,and the detection length was 250 bp.The overall methylation levels of MAOA＿1 fragments in the SCZ group and the control group in the overall samples were similar,and there was no significant difference(P =0.4072).In gender stratification analysis,methylation of MAOA＿1 fragment in male SCZ groups was significantly higher than that in the control group(P = 0.0142).The methylation level of MAOA＿1 fragment in the female SCZ group was significantly lower than that in the control group(P = 0.0273),and there was gender difference. The MAOA＿2 fragment was located in the Chr X:43515466-43515218 region,1064 bp from the transcription initiation site,and the detection length was 249 bp.The overall methylation levels of MAOA＿2 fragments in the SCZ group and the control group in the overall samples were similar,and there was no significant difference(P =0.4821).After sex stratification analysis,the methylation level of MAOA＿2 fragment in the male SCZ group was significantly higher than that in the control group(P = 0.0204).The methylation levels of MAOA＿2 fragments in the female SCZ group were generally similar to those in the control group without significant difference(P = 0.1892).3.Correlation between methylation level of Cp G site in MAOA gene and SCZ The MAOA＿1 fragment contained 16 Cp G sites,among which the SCZ groups at MAOA＿1＿Cp G1,Cp G2,Cp G3,Cp G4,Cp G6,Cp G7,Cp G8,Cp G9,Cp G12,Cp G13,Cp G14 and Cp G16 sites were higher than the control group with significant differences(P < 0.05),and the significant differences among groups disappeared after Bonferroni correction.After sex stratification analysis,the methylation levels of MAOA＿1＿Cp G1,Cp G2,Cp G4,Cp G6,Cp G7,Cp G11,Cp G13,Cp G14,Cp G15 and Cp G16 in the male SCZ group were significantly higher than those in the control group(P < 0.05).The methylation levels of MAOA＿1＿Cp G1,Cp G3,Cp G4,Cp G5,Cp G12,Cp G13,Cp G14,Cp G15 and Cp G16 in the female SCZ group were significantly lower than those in the control group(P < 0.05),indicating that there were gender differences. The MAOA＿2 fragment contained 13 Cp G sites,among which the SCZ groups with MAOA＿2＿Cp G1,Cp G3,Cp G5,Cp G6,Cp G7,Cp G9,Cp G10,Cp G11,Cp G12 and Cp G13 sites were higher than the control group with a significant difference(P <0.05),and the significant difference disappeared between the two groups after correction by Bonferroni.According to gender stratification analysis,the methylation levels of MAOA＿2＿Cp G2,Cp G3,Cp G5,Cp G6,Cp G7,Cp G9,Cp G10,Cp G11,Cp G12 and Cp G13 sites in the male SCZ group were significantly higher than those in the healthy control group(P < 0.05).The methylation levels of MAOA＿2＿Cp G2 and Cp G6 sites in the female SCZ group were significantly lower than those in the control group(P < 0.05),and there was gender difference.4.Correlation between methylation level of COMT gene fragment and SCZ A total of 1 target fragment was detected for DNA methylation in the promoter region of COMT gene.The COMT gene promoter fragment was located in the Chr22:19929117-19929359 region,146 bp from the transcription initiation position and243 bp in length.The overall DNA methylation levels in the SCZ group were similar to those in the control group,and there was no significant difference(P > 0.05).Through gender stratification analysis,there was no significant difference between the sexes in the same group(P > 0.05).5.Correlation between methylation level of Cp G site of COMT gene and SCZ The promoter fragment of COMT gene contained 32 Cp G sites.There was no significant difference in the overall sample size of 32 Cp G sites between the SCZ and control groups(P > 0.05).Through gender stratification analysis,there was gender difference in the methylation levels of Cp G sites in COMT fragments between the SCZ group and the control group.The methylation levels of COMT＿Cp G7(P =0.0364)and COMT＿Cp G22(P = 0.0253)loci in the male SCZ group were significantly lower than those in the control group.The levels of methylation at the COMT＿Cp G14(P =0.0434)and COMT＿Cp G31(P = 0.0349)sites in the female SCZ group were significantly higher than those in the control group.Conclusion(s):1.The methylation levels of Cp G sites in the promoter region of MAOA gene were associated with schizophrenia and showed gender differences.Among them,the hypermethylation of Cp G sites may increase schizophrenia in males and decrease schizophrenia in females.2.The methylation levels of Cp G sites in the promoter region of COMT gene were associated with schizophrenia with gender differences.Different epigenetic influencing factors may exist in schizophrenia of different sexes. |
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