Association Between The AS3MT Gene Methylation And Schizophrenia

Objective: Schizophrenia is a severe mental illness that causes a considerable disease burden and seriously endangers human health.In this study,we sought and discovered epigenetic markers in schizophrenia patients by comparing the differences in DNA methylation levels of AS3 MT gene promoter region in peripheral blood lymphocytes of schizophrenia patients and the average population and analyzed the relationship between AS3 MT promoter region DNA methylation and cognitive function,psychopathological symptoms,and social function in schizophrenia patients.This study aims to clarify the pattern of methylation regulation in the promoter region of the AS3 MT gene and provide a theoretical basis for the etiology of schizophrenia.Methods: 15 patients with schizophrenia who were hospitalized in Shandong Daizhuang Hospital between July 2021 and July 2022 were selected as the case group.15 normal healthy individuals matched with the case group in terms of age and gender were selected as the control group.The age,sex,years of education and marital status of the case and control groups were investigated using a self-administered sociodemographic questionnaire;the social function of the case group was assessed using the global assessment of function scale;the psychopathological symptoms of the case group were assessed using the Positive and Negative Symptom Scale;the cognitive function of the case and control groups was assessed using the Chinese version of the MATRICS consensus cognitive battery;extract 5ml of peripheral venous blood from the case and control groups,and detect the DNA methylation level in the promoter region of AS3 MT gene by pyrophosphate sequencing technology.The data were analyzed using SPSS 25.0 software.Results:1.The differences in the methylation levels of the cg02921697(P=0.004),cg08856941(P=0.026),cg11050480(P=0.026),cg11784071(P=0.036),and cg24592962(P=0.001)in the promoter region of the AS3 MT gene between the case and control groups were statistically significant.The methylation levels in the case group were lower than those in the control group.2.The differences in the scores of the continuous performance testidentical pairs(P=0.042),spatial span(P=0.015),symbol coding(P=0.012),category fluency(P=0.026),verbal learning and memory(P=0.013),mazes test(P<0.001),and managing emotions(P=0.007)between the case and control groups were statistically significant,and the scores of the case group were all lower than those of the control group.3.The cg11784071(P=0.025)in the promoter region of the AS3 MT gene in schizophrenia patients was negatively associated with the total PANSS score,and the cg24592962(P=0.041)was negatively associated with the PANSS positive score.4.The methylation level of the cg02921697 in the promoter region of the AS3 MT gene in schizophrenia patients was positively correlated with the spatial span(P=0.036),trail making test(P=0.001),category fluency(P=0.004),visual learning and memory(P<0.001),and mazes test(P=0.006).The methylation level of the cg08856941 was positively correlated with the spatial span(P=0.010),and trail making test(P=0.013).The methylation level of the cg11050480 was positively correlated with the continuous performance test-identical pairs(P=0.032),spatial span(P<0.001),trail making test(P=0.009),symbolic coding(P=0.017),category fluency(P=0.019),verbal learning and memory(P=0.020),visual learning and memory(P=0.031),and mazes test(P=0.019).The methylation level of the cg11784071 was positively correlated with the trail making test(P=0.014),symbolic coding(P=0.024),verbal learning and memory(P=0.009),and visual learning and memory(P=0.001).The methylation level of the cg24592962 was positively correlated with the trail making test(P=0.003),visual learning and memory(P=0.024),and mazes test(P=0.032).The methylation level of the cg25143771 was positively correlated with the spatial span(P=0.007),trail making test(P=0.028),symbolic coding(P=0.017),verbal learning and memory(P=0.034),visual learning and memory(P=0.006)and mazes test(P=0.033).Conclusion:1.The differences in the methylation levels of cg02921697,cg08856941,cg11050480,cg11784071,cg24592962,and cg25143771 in the promoter region of the AS3 MT gene between schizophrenia patients and healthy individuals were statistically significant,and all 6 Cp G sites were less methylated in schizophrenia patients than in controls.2.Patients with schizophrenia performed worse than healthy individuals on 6 dimensions of cognitive functioning: verbal learning and memory,working memory,speed processing,attention/vigilance,social cognition,and reasoning and problem-solving.3.The lower the methylation level of the AS3 MT gene cg11784071 in schizophrenia patients,the more severe the psychopathological symptoms may be.The lower the methylation of the cg24592962,the more severe the positive symptoms may be.4.The methylation level of the cg02921697,cg08856941,cg11050480,cg11784071,cg24592962,and cg25143771 in the promoter region of the AS3 MT gene in schizophrenia patients was independently associated with multiple dimensions of cognitive function.