Understanding Parkinson’s disease is like exploring a mysterious jungle where genetics, lifestyle, and environmental factors interact. Scientists have discovered that DNA methylation, specifically of GPNMB cg17274742, plays a role in the onset of the disease. Picture a transmembrane protein called GPNMB as a crucial guide in this jungle, helping immune cell activation and maturation. The research from Taiwan Biobank focuses on how exercise and gender impact the regulation of GPNMB cg17274742 methylation levels. By analyzing data from over 2,400 participants, the study found that exercise significantly influences methylation levels in males but not in females. In fact, exercising men had lower methylation levels compared to female and non-exercising reference groups. These findings highlight the importance of exploring gender-specific and exercise-related factors in understanding Parkinson’s disease risk. Further research is needed to unravel the underlying mechanisms and implications of these epigenetic changes. Excitingly, this study offers new insights into potential strategies for preventing and managing Parkinson’s disease!

BackgroundParkinson’s disease (PD) is a complex neurodegenerative disease with an elusive etiology that involves the interaction between genetic, behavioral, and environmental factors. Recently, epigenetic modifications, particularly DNA methylation, have been recognized to play an important role in the onset of PD. Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane protein crucial for immune cell activation and maturation, has emerged as a potential biomarker for the risk of PD. This research aims to investigate the influence of exercise and gender on the regulation of methylation levels of GPNMB cg17274742 in individuals.MethodsWe analyze data from 2,474 participants in the Taiwan Biobank, collected from 2008 and 2016. Methylation levels at the GPNMB cg17274742 CpG site were measured using Illumina Infinium MethylationEPIC beads. After excluding individuals with incomplete data or missing information on possible risk factors, our final analysis included 1,442 participants. We used multiple linear regression models to assess the association between sex and exercise with adjusted levels of GPNMB cg17274742 for age, BMI, smoking, drinking, coffee consumption, serum uric acid levels, and hypertension.ResultsOur results demonstrated that exercise significantly influenced the methylation levels of GPNMB cg17274742 in males (β = −0.00242; p = 0.0026), but not in females (β = −0.00002362; p = 0.9785). Furthermore, male participants who exercised showed significantly lower levels of methylation compared to the reference groups of the female and non-exercising reference groups (β = −0.00357; p = 0.0079). The effect of the interaction between gender and exercise on the methylation of GPNMB cg17274742 was statistically significant (p = 0.0078).ConclusionThis study suggests that gender and exercise can modulate GPNMB cg17274742, with hypomethylation observed in exercise men. More research is needed to understand the underlying mechanisms and implications of these epigenetic changes in the context of risk and prevention strategies.

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