Study On The Correlation Between SLC6A4 Gene Methylation And Violent Aggressive Behavior Of Mentally Healthy Individuals And Schizophrenia Patients

Objective:To investigate the correlation between the DNA methylation level of the promoter region of the SLC6A4 gene in Yunnan Han males and the violent attacks of mental health individuals and schizophrenia patients,Reveal the genetic basis of violent aggressive behavior of individuals with different mental states,Provide a theoretical basis for the prevention and control of violent attacks.Methods:1.This study collected 61 men who were imprisoned for the crime of intentional homicide,Intentional injury or robbery with mental health violent assault individuals(mental health individual violent assault group)、56 male schizophrenia patients with violent aggressive behavior(violent assault group of schizophrenia patients)and 60 male healthy controls(healthy control group);2.Mental health individuals violent attack group and healthy control group used Buss&Perry Attack Scale and Barratt Impulse Scale to assess their aggressiveness and impulsivity,The violent assault group for schizophrenia adopts the "Central Subsidy Local Health Funds Severe Mental Illness Management and Treatment Project" established by the China Centers for Disease Control and Prevention to determine the aggression risk and overall risk of serious mental illness;3.Collect 4ml of peripheral blood,store in EDTA anticoagulation tube,store at-80℃.Use QIAamp DNA Blood Mini Kit to extract DNA from peripheral blood samples,Treat samples with EZ DNA Methylation-Gold Kit bisulfite,The fragment length distribution of the library is verified by Agilent 2100 Bioanalyzer,Use the Illumina Hiseq platform to detect the DNA methylation status of the target fragment in the promoter region of the SLC6A4 gene and the 17 CpG sites it contains,Use SPSS 25.0 for data statistical analysis.Result:1.The overall comparison of mental health individual violent attack group,schizophrenic violent attack group and healthy control group:(1)The average age is 40.30±12.35 years old,44.00±11.65 years old and 39.15±10.25 years old,three groups of samples There is no significant difference in age between the two groups(P=0.062);(2)The DNA methylation level of the target fragment in the promoter region of the SLC6A4 gene has a significant difference among the three groups(Welch F=0.018<0.05);(3)Among the 17 CpG sites contained in the target fragment of the SLC6A4 gene,10 CpG sites are significantly different in the overall comparison:CpG3,CpG4,CpG6,CpG7,CpG8,CpG9,CpG10,CpG12,CpG14,CpG 15.Corrected by Bonferroni,CpG4,CpG8,CpG10,CpG12,CpG14 are still significant,and CpG3,CpG6,CpG7,CpG9,CpG15 are significant disappeared;(4)There were significant differences in the overall comparison of the DNA methylation level of the target segment in the promoter region of the SLC6A4 gene between the three groups of study subjects in different education levels/unmarried/smoking(P<0.05).2.Pairwise comparison between the violent attack group of schizophrenia patients and the healthy control group:(1)The DNA methylation level of the target fragment in the promoter region of the SLC6A4 gene has a significant difference between the two groups(P=0.024);(2)Among the 10 CpG sites that have overall differences among the three groups of SLC6A4 gene target fragments,6 sites are still significant:CpG3,CpG4,CpG8,CpG12,CpG14,CpG15,and the methylation level shows schizophrenia The violent attack group of patients with symptom is higher than the healthy control group.The remaining 4 CpG sites:CpG6,CpG7,CpG9,CpG10 methylation levels were not statistically significant.After Bonferroni correction,the significance of the above-mentioned sites disappeared.(3)In the comparison between the violent attack group of schizophrenia patients and the healthy control group,the distribution difference between unmarried and married(χ2=6.658,P=0.010)was statistically significant.The Logistic regression model showed that the violent attack group of schizophrenia patients The risk of violent aggressive behavior in unmarried groups is higher than that in married groups(OR=0.283,95%CI:0.111-0.721).(4)Comparison of the violent attack group and healthy control group of schizophrenic patients under different environmental factors found that in the smoking group The difference in the methylation level of the target segment of the SLC6A4 gene between the two groups of subjects was significant(P<0.05),and the methylation level of the violent attack group of schizophrenia patients was higher than that of the healthy control group.And the difference among unmarried groups was not statistically significant.3.Pairwise comparison between mental health individual violent attack group and healthy control group:(1)There was no statistically significant difference in the DNA methylation level of the target fragment in the promoter region of the SLC6A4 gene between the two groups.(2)The 10 CpG sites with overall differences among the three groups of SLC6A4 gene target fragments showed no statistically significant difference in site methylation levels between the two groups(P>0.05).(3)The total scores of the Buss&Perry Attack Scale and the other four subscales of the violence attack group of mental health individuals were significantly higher than those of the healthy control group(P<0.001).Except for the Barratt Impulsivity Scale,the scores of cognitive impulsivity were not statistically different between the violent attack group and the healthy control group.The scores of the total scale and the other two subscales of the mental health individual violent attack group were higher than those of the healthy control group(p<0.01).(4)In the comparison between the mental health individual violent attack group and the healthy control group,the distribution difference between the high education level and the low education level was statistically significant(χ2=16.688,P<0.001).The Logistic regression model showed that violent attacks occurred in the low education group The risk of behavior is higher than that of the highly educated group(OR=0.095,95%CI:0.027-0.341).(5)There was no statistically significant difference in the methylation level of the target segment of the SLC6A4 gene between the mental health individual violent attack group and the healthy control group in different risk factor groups(P>0.05).4.Pairwise comparison between the violent attack group of mental health individuals and the violent attack group of schizophrenia patients:(1)There is a significant difference in the DNA methylation level of the target segment of the SLC6A4 gene promoter region in the comparison between the two groups(P=0.018));(2)Among the 10 CpG sites with overall differences among the three groups of SLC6A4 gene target fragments,3 sites still have significant differences:CpG4,CpG10,CpG 14,the methylation level showed that the violent attack group of schizophrenia patients was higher than the violent attack group of mentally healthy individuals.The remaining 7 CpG sites:CpG3,CpG6,CpG7,CpG8,CpG9,CpG12,CpG15 There was no statistically significant difference in methylation level.After Bonferroni correction,the significance of the above-mentioned sites disappeared.(3)In the comparison between the violent attack group of patients with schizophrenia and the violent attack group of mental health individuals,the high educational level and low educational level(χ2=6.523,P=0.011)and smoking and non-smoking(χ2=10.177,P<0.001)The difference in the distribution of is statistically significant.The Logistic regression model shows that the low-education groups in the mental health individual violent attack group are at higher risk of violent aggressive behavior(OR=0.209,95%CI:0.061-0.714),and the smoking group has aggressive behavior The risk is 4.187 times that of non-smokers(OR=4.187,95%CI:1.677-10.453).(4)The comparison between the violent attack group of mental health individuals and the violent attack group of schizophrenia patients under different environmental factors found that in the low education(P=0.024),unmarried(P=0.028),and smoking(P=0.014)groups The difference in the methylation level of the target segment of the SLC6A4 gene is significant,and the methylation level of the target segment of the SLC6A4 gene shows that the violent attack group of schizophrenia patients is higher than the violent attack group of mentally healthy individuals,while in the high-educated group The difference was not statistically significant(P=0.945).Conclusion:1.There is no significant correlation between the methylation status of SLC6A4 gene and the violent aggressive behavior of mental health individuals.It may have an impact on the violent aggressive behavior of Yunnan Han male patients with schizophrenia.Research suggests that the target segment of the SLC6A4 gene promoter and CpG3,CpG4,The hypermethylation status of CpG8,CpG12,CpG14,and CpG15 may be more aggressive.2.Schizophrenia violent attack and mental health individual violent attack group may have different epigenetic basis.The target segment of SLC6A4 gene promoter region and the methylation status of CpG4,CpG10,CpG 14 locus are in the violent attack of male mental health individuals.There is a significant difference between the violent attack between the group and the schizophrenic patients.