Cardiovascular

Alu hypomethylation in ischemic stroke: Associations with selected clinical characteristics.

TL;DR

Ischemic stroke patients had significantly lower overall Alu methylation than healthy controls, an association that persisted after adjustment for age and sex, but the cross-sectional design does not establish causality, disease progression, or predictive or prognostic value.

Key Findings

Ischemic stroke patients had significantly lower overall Alu methylation than healthy controls.

  • The study compared 85 ischemic stroke patients with 50 healthy controls.
  • Alu methylation was measured with Alu-Combined Bisulfite Restriction Analysis (COBRA), a quantitative approach.
  • The difference was reported as P < 0.0001.

Alu methylation was negatively correlated with age in both controls and stroke patients, with a stronger correlation in controls.

  • Controls: r = -0.6131, P < 0.0001.
  • Ischemic stroke patients: r = -0.2834, P = 0.0086.

The difference in Alu methylation between stroke patients and controls remained among age-matched participants.

  • In the age-matched comparison, control and ischemic stroke patients still differed (P = 0.0182).

Lower 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.

Disease duration was not correlated with Alu methylation in unadjusted analysis, but longer duration was associated with lower methylation after adjustment for age and sex.

  • Unadjusted: r = -0.1594, P = 0.1450.
  • Adjusted for age and sex: β = -0.556, 95% CI = -0.994 to -0.117, P = 0.0137.

Alu methylation was lower in patients with multiple stroke events and with Fazekas scores of 2-3 in unadjusted comparisons, but these associations were not significant after adjustment for age and sex.

  • Multiple stroke events: unadjusted P = 0.0323; adjusted P = 0.0542.
  • Fazekas scores 2-3: unadjusted P = 0.0324; adjusted P = 0.0684.

Stroke circulation location was not associated with Alu methylation.

  • No significant association was found between circulation location of the stroke and Alu methylation levels.

The authors state the cross-sectional design limits interpretation of the findings.

  • The design does not establish causality, disease progression, or predictive or prognostic value.
  • Longitudinal studies are needed to determine clinical relevance.

What This Means

This study looked at Alu methylation, a chemical marking on repetitive stretches of DNA, in the blood of 85 people with ischemic stroke and 50 healthy people. Stroke patients had lower Alu methylation overall. Methylation also declined with age in both groups, but the difference between patients and controls remained when the authors compared age-matched people and when they statistically adjusted for age and sex. Within the stroke group, people who had had the disease longer tended to have lower Alu methylation once age and sex were accounted for. Patients with multiple strokes or more brain white-matter changes (Fazekas scores 2-3) also showed lower methylation in simple comparisons, but these links were no longer statistically significant after adjustment. The location of the stroke in the brain's circulation was not related to methylation. This research suggests Alu methylation is associated with having had an ischemic stroke. Because the study captured one point in time, it cannot show whether low methylation causes stroke, results from it, or can predict outcomes. Longer-term studies that follow people over time are needed to learn whether this has any clinical use.

Have a question about this study?

Citation

Siri-Archawawat D, Chuaijit S, Mutirangura A, Tan J, Thongsroy J. (2026). Alu hypomethylation in ischemic stroke: Associations with selected clinical characteristics.. PloS one. https://doi.org/10.1371/journal.pone.0360371