Alu hypomethylation in ischemic stroke: Associations with selected clinical characteristics

This study investigated Alu methylation levels in 85 ischemic stroke patients and 50 healthy controls, using Alu-Combined Bisulfite Restriction Analysis (COBRA) a quantitative approach to assess methylation. Ischemic stroke patients had significantly lower overall Alu methylation as compared to controls (P < 0.0001). Alu methylation was negatively correlated with age in both the control group (r = -0.6131, P < 0.0001) and the ischemic stroke group (r = -0.2834, P = 0.0086). Moreover, among age-matched ischemic stroke patients, there remained a difference between control and ischemic stroke patients (P = 0.0182). Alu methylation remained associated with ischemic stroke status after adjustment for age and sex (adjusted OR = 0.841, 95% CI = 0.709-0.979, P = 0.0327). Within the ischemic stroke group, disease duration was not significantly correlated with Alu methylation in the unadjusted analysis (r = -0.1594, P = 0.1450). However, after adjustment for age and sex, longer disease duration was associated with lower Alu methylation (β = -0.556, 95% CI = -0.994 to -0.117, P = 0.0137). Alu methylation was lower in patients with a history of multiple stroke events (P = 0.0323) and in those with Fazekas scores of 2-3 (P = 0.0324) in the unadjusted comparisons, but neither association remained statistically significant after adjustment for age and sex (P = 0.0542 and P = 0.0684, respectively). Stroke circulation location was not associated with Alu methylation. These findings support an association between Alu methylation and ischemic stroke status. Longer disease duration was also associated with lower Alu methylation after adjustment for age and sex. However, the cross-sectional design does not establish causality, disease progression, or predictive or prognostic value. Longitudinal studies are needed to determine the clinical relevance of these findings.