The Association Study Between TPH2 Gene Promote Methylation Modification And Obsessive-compulsive Disorder

Objective:Obsessive-compulsive disorder is characterized by uncontrollable obsession and compulsive behavior.When the symptoms develop to severity,they will obviously affect the social function of the patients,such as study,work,family,etc.The purpose of this study was to investigate the correlation between DNA methylation modification and obsessive-compulsive disorder in the promoter region of TPH2 gene,and whether the methylation level of DNA in the promoter region could affect the severity of obsessive-compulsive disorder.Methods:From May 2018 to February 2021,95 patients with obsessive-compulsive disorder were admitted to Shandong Mental Health Center and 99 normal controls were collected,A total of 194 cases,It was divided into compulsive disorder group and control group.The DNA methylation levels in the promoter region of TPH2 gene in peripheral blood of the two groups were detected by mass spectrometry,and the DNA methylation levels at each CPG site in the promoter region of TPH2 gene in all samples were analyzed,as well as the differences in the DNA methylation levels of each CPG site in the promoter region of TPH2 gene in peripheral blood were analyzed.Binary logistic regression analysis was used to adjust the mixed risk factors to observe whether DNA methylation level in the promoter region of TPH2 gene in peripheral blood could be used as an independent risk predictor of compulsive disorder.Pearson was used to test the correlation between the methylation level of CpG＿5 and CpG＿6 in the promoter region of TPH2 gene and the severity of compulsive disorder in han Chinese population.Results :1.The DNA methylation level of CpG＿4 sites in the promoter region of the two groups was the highest,among which CpG＿4、CpG＿5、CpG＿6 sites showed statistically significant differences in DNA methylation levels between the two groups(P<0.05),suggesting higher methylation of gene promoter CpG＿6 sites in OCD samples,while the methylation rate of CpG＿4 and CpG＿5sites was lower than that of normal group.At a significant level of 0.05,The methylation level of TPH2 gene CpG＿5 sites was negatively correlated with obsessive compulsive disorder,A OR value of 0.951,95% CI=0.905～0.999,P<0.045;At a significant level of 0.01,There was a weak positive correlation between CpG＿6 methylation levels of TPH2 genes and obsessive compulsive disorder,A OR value of 1.039,95% CI=1.010-1.068,P<0.007.There was no correlation between the methylation level of TPH2 gene CpG＿5、CpG＿6 locus and the score of forced thinking,forced behavior and forced total score of OCD patients’ Ya-BOCS scale(P>0.05)Conclusion :1.The level of DNA methylation at the site CpG＿4、CpG＿5、CpG＿6 was related to compulsive disorders in the promoter region of TPH2 gene in the han population of northern China.2.The hypermethylation of CpG＿5 sites in the promoter region of TPH2 gene is a protective factor for obsessive-compulsive disorder in Chinese Han population,and hypermethylation of CpG＿6 sites is a risk factor for obsessive-compulsive disorder in Chinese Han population.3.The methylation level of CpG＿5、CpG＿6 sites in the promoter region of TPH2 gene was not significantly correlated with the severity of obsessive-compulsive disorder in Chinese Han population.