| Summary: | Increased ventilation during exercise in polluted areas could trigger airway inflammation. We evaluated blood DNA methylation of the SOX2-promoter region in relation to exercise and PM<sub>2.5</sub> in Taiwanese adults. Data of 948 participants aged 30−70 years were retrieved from the Taiwan Biobank Database (2008−2015) and the Air Quality Monitoring Database (2006−2011). PM<sub>2.5</sub> was positively associated with SOX2-promoter methylation (β = 0.000216; <i>p</i> < 0.0001). The interaction between PM<sub>2.5</sub> and exercise on SOX2-promoter methylation was significant (<i>p</i> = 0.0146). After stratification by exercise habits, PM<sub>2.5</sub> was positively associated with SOX2 methylation in only individuals who did regular exercise (β = 0.0003490; <i>p</i> < 0.0001). After stratification by exercise habits and residential areas, SOX2-promoter methylation levels in those who lived in the southern area were higher for both the regular exercise (β = 0.00272; <i>p</i> = 0.0172) and no regular exercise groups (β = 0.002610 and <i>p</i> = 0.0162). SOX2-promoter methylation levels in those who lived in the northern area and did regular exercise were lower; β = -0.00314 (<i>p</i> = 0.0036). In conclusion, PM<sub>2.5</sub> was positively associated with SOX2-promoter methylation in participants who did regular exercise. Living in the southern area was positively associated with SOX2-promoter methylation regardless of exercise habits.
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