| Objective: The causes and pathogenesis of schizophrenia are unclear,with genetic and environmental factors playing a major role in its development.Epigenetic modifications are an important mechanism mediating the interaction of genetic and environmental factors.Previous studies have shown that the SETD1 A gene is significantly associated with schizophrenia,but how this gene is involved in the pathogenesis of schizophrenia is unclear.In this study,we analyzed whether DNA methylation modifications in the promoter region of the SETD1 A gene were associated with schizophrenia by comparing the differences in DNA methylation levels in the promoter region of the SETD1 A gene in peripheral blood lymphocytes from schizophrenia patients and normal populations,and further investigated the association between the promoter region DNA methylation levels of the SETD1 A gene and psychopathological symptoms and cognitive function in schizophrenia patients.The aim was to analyze the role of epigenetic regulation of SETD1 A gene in the pathogenesis of schizophrenia at the level of DNA methylation.Methods: A total of 30 samples were collected（15 in the schizophrenia group and 15 in the control group）,of which the schizophrenia group were schizophrenia patients who met the DSM-IV diagnostic criteria and the control group were normal healthy individuals who were roughly matched with the schizophrenia group in terms of age and gender from October 2020 to July 2021 at the inpatient of Shandong Daizhuang Hospital.The age,sex,and years of education of the subjects in both groups were recorded using a self-administered general demographic questionnaire;the clinical symptoms of the schizophrenia group were assessed using the PANSS,and the GAF to assess overall functioning in the schizophrenia group;and the cognitive function of the two groups was assessed using the Chinese version of the MCCB;peripheral venous blood was extracted from the two groups,and DNA methylation levels in the promoter region of the SETD1 A gene were detected using pyrosequencing.The age,gender,years of education,cognitive function,and cognitive function of the two groups were analyzed using SPSS 26.0 software.The correlation between the DNA methylation level of the promoter region of SETD1 A gene and the clinical symptom scale score in the schizophrenia group,the correlation between the DNA methylation level of the promoter region of SETD1 A gene and the cognitive function score was analyzed using SPSS 26.0 software.The statistical analysis methods for the comparison of differences between two groups were chosen from chi-square test,independent sample t-test or nonparametric Mann-Whitney U test,and the statistical analysis methods for the correlation analysis between two groups were chosen from Pearson correlation analysis,Spearman correlation analysis or partial correlation analysis.Results:1.The difference in scores on the trail making test（Z=-3.156,P=0.002）,symbol coding（t=-0.721,P<0.001）,category fluency（t=-3.229,P=0.003）,continuous performance test-identical pairs（t=-3.765,P=0.001）,spatial span（t=-4.203,P<0.001）,Hopkins verbal learning test-revised（t=-4.065,P<0.001）,brief visuospatial memory test-revised（t=-2.851,P<0.001）,maze test（t=-5.920,P<0.001）,and emotion management（t=-2.648,P=0.013）in the MCCB between the schizophrenia group and the control group was statistically significant,suggesting that the schizophrenia group scored lower on the above tests than the normal group.2.The difference in DNA methylation levels at the cg01191788（t=-2.860,P=0.008）,cg03087852（t=-3.523,P=0.001）,cg03532420（t=-2.343,P=0.026）,cg04033451（t=-2.436,P=0.021）,cg05102288（t=-3.388,P=0.002）,cg06403422（t=-2.823,P=0.009）,cg12703078（t=-3.026,P=0.005）,cg23942803（t=-2.975,P=0.006）in the promoter region of the SETD1 A gene between the schizophrenia group and the control group was statistically significant,suggesting that the schizophrenia group had lower DNA methylation levels at the above locus than the normal group.3.The level of methylation at the cg04033451 in the promoter region of the SETD1 A gene was moderately negatively correlated with positive symptom scores of PANSS（r=-0.596,P=0.019）.4.The methylation level of the cg01191788 in the promoter region of the SETD1 A gene was moderately positively correlated with the symbol coding score（r=0.476,P=0.008）,the spatial span score（r=0.419,P=0.021）,the brief visuospatial memory test-revised score（r=0.446,P=0.013）,and maze test scores（r=0.381,P=0.038）;The methylation level of the cg05102288 showed moderate positive correlation with category fluency（r=0.365,P=0.047）,emotion management scores（r=0.366,P=0.047）.The methylation level of the cg06403422 was moderately positively correlated with category fluency scores（r=0.365,P=0.047）.The methylation level of the cg12703078 was moderately positively correlated with Hopkins verbal learning test-revised scores（r=0.410,P=0.025）,and brief visuospatial memory test-revised scores（r=0.385,P=0.036）.Conclusion:1.Cognitive functioning（including the 7 dimensions of speed processing,attention/vigilance,working memory,verbal learning and memory,visual learning and memory,reasoning and problem solving,and social cognition）is generally lower in people with schizophrenia than in normal healthy populations.2.The methylation levels of cg01191788,cg03087852,cg03532420,cg04033451,cg05102288,cg06403422,cg12703078,cg23942803 loci in the promoter region of SETD1 A gene were associated with schizophrenia,and the methylation levels of the above loci in schizophrenia patients methylation levels were low relative to healthy individuals.3.The lower methylation level of the cg04033451 locus in the promoter region of the SETD1 A gene in schizophrenia patients,the more severe their positive symptoms.4.The methylation levels of cg01191788,cg05102288,cg06403422,and cg12703078 sites in the promoter region of the SETD1 A gene were significantly correlated with cognitive function. |
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