【Abstract】Objective To observe the alterations in the methylation of brain derived neurotrophic factor (BDNF) gene promoter region and its expression level in peripheral blood of Parkinson′s disease (PD) patients, and analyze their correlation in order to explore the pathogenesis of PD from the perspective of epigenetic regulation. Methods A total of 54 PD patients (PD group) admitted to the First Affiliated Hospital of Baotou Medical College from September 2020 to October 2023 were enrolled, and another 51 healthy individuals who taking physical examination in the hospital during same period served as control group. Methylation-specific polymerase chain reaction (MS-PCR) was applied to assess the methylation status of peripheral BDNF promoter, and quantitative real-time polymerase chain reaction (Q-PCR) was conducted to determine the mRNA expression of BDNF in peripheral blood. SPSS statistics 20.0 was used for data analysis. Depending on data type, t test or Mann-Whitney U test was used for inter-group comparison. Spearman rank correlation analysis was employed to analyze the correlation between the methylation level of BDNF gene promoter region and mRNA expression. Pearson correlation analysis was utilized to analyze the correlation of BDNF mRNA level with the total score, motor symptom score and non-motor symptom score of unified Parkinson′s disease rating scale (UPDRS). Binary logistic regression model was built to identify the influencing factors for PD incidence. Results The methylation rate of peripheral BDNF promoter was significantly higher in the PD group than the control group, and the rate was also higher in the PD patients in mid-to-late stage than those in early stage (P<0.05). The PD patients exhibited significantly lower expression level of peripheral blood BDNF than the control group, and the level was notably lower in mid-to-late-stage PD patients than the early-stage PD patients (P<0.05). In PD group, the mRNA level of BDNF in peripheral blood was negatively correlated with its promoter methylation level (r=-0.928; P<0.001), and the total score, motor symptom score and non-motor symptom score of UPDRS (r=-0.461, -0.429, -0.298; P<0.05). Binary logistic regression analysis showed that the methylation status of BDNF promoter was a risk factor for PD (OR=3.887,95%CI 1.035-14.597; P=0.044), and triglyceride was a protective factor for PD (OR=0.392,95%CI 0.155-0.997; P=0.049). Conclusion In PD patients, peripheral BDNF promoter is abnormally hypermethylated, its mRNA expression is down-regulated, and there is a negative correlation between the two indicators. It is suggested that abnormal promoter hypermethylation of BDNF may be involved in the occurrence and development of PD by down-regulating its expression.

This work was supported by the Natural Science Foundation of Inner Mongolia Autonomous Region ( 2021MS08053), the Project of Health Science and Technology Plan of Inner Mongolia Autonomous Region (202201422), and the Youth Science and Technology Talent Development Plan of Baotou Medical College (BYJJ-DXK 2022042).