Objective: This research aims to dissect the influence of physical activity and circadian rhythms on neuroinflammation and neurodegenerative disease progression, focusing on Parkinson’s Disease (PD).

Background: The GPNMB gene, linked to PD risk, produces an anti-inflammatory protein. Its expression in PD is associated with cg172747472 hypomethylation near GPNMB. Our findings suggest that the PER2 rs2304672 GC+CC genotype, which influences circadian regulation, interacts with physical activity to reduce methylation at cg172747472. This advocates for the importance of exercise and circadian rhythm regulation in neurodegenerative disease management.

Method: There were 2,352 participants and we excluded incomplete or missing values (n=993), finally, there were 1,359 analytic participants enrolled in this study. Multiple linear regression models were used to determine the association of exercise, cg17274742, and rs2304672 genotypes. The Chi-square test was performed to demonstrate the differences between exercise and categories (rs2304672, gender, age, BMI, cigarette smoking, alcohol intake, hypertension, vegetarian, and caffeine intake).

Results: There were 1359 participants overall who met the inclusion criteria of the study, female and male were 710 and 649 respectively. The mean ± standard error (SE) GPNMB cg17274742 methylation level (beta value) in no exercise and exercise were 0.949 ± 0.0004 and 0.948 ± 0.0005, respectively. 

    There was an interaction between the PER2 rs2304672 variant and exercise (p=0.0496) with cg17274742 methylation (Table 1). From Table 2, the association of rs2304672, exercise, and cg17274742 was demonstrated by four rs2304672 and exercise groups. The reference group was rs2304672 GC+CC and no exercise, rs2304672 GC+CC and exercise was associated with cg17274742 methylation level (ꞵ = -0.00422; P-value = 0.0105). The group with rs2304672 GG and exercise was also significantly related to lower cg17274742 methylation level (ꞵ = -0.00257; P-value = 0.0335). However, rs2304672 GG and no exercise was not associated with cg17274742 methylation (ꞵ = -0.00177; 0.1343).

Conclusion: Those who had rs2304672 GC+CC genotype and regular exercise might lower the cg17274742 methylation level and increase the expression of the GPNMB gene which is an important neuroinflammatory-related PD risk variant.

Table 1

Table 2

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/exercise-mitigates-dna-methylation-changes-at-cg17274742-associated-with-the-circadian-gene-variant-per2-rs2304672-a-biobank-analysis/