DNA Methylation of the ABCA1 and ABCG1 Genes Contributes to Stroke Risk

Stroke is a major cause of death in China. The epigenetic factors, especially the methylation of ABCA1/G1 genes implicated in cholesterol regulation, are being examined to comprehend their association with stroke.

In this nested case-control study, we examined data from the Northwest China Cohort (CNC-NX) initial phase. During follow-up, 63 incident stroke cases were identified, of which 10 were excluded due to predefined criteria (e.g., cancer, severe infections, or missing baseline/follow-up blood samples). After 1:1 matching by age, sex, ethnicity, and residence, 53 case-control pairs were initially enrolled. However, due to DNA degradation in long-term stored samples, only 35 matched pairs were ultimately included for analysis. All participants were adults aged ≥18 years. We used conditional logistic regression models to determine the odds ratio (OR) and 95% confidence interval (95% CI) for stroke occurrence.

CpG_10.11.12.13 methylation levels in ABCA1 were associated with stroke risk (OR 0.93, 95% CI: 0.87-0.99), and dynamic changes in CpG_19.20 methylation levels in ABCG1 were associated with stroke risk (OR 1.62, 95% CI: 1.11-2.37). In dynamic methylation, high methylation levels of CpG_19.20 in ABCG1 were associated with a 5.10 times higher risk of stroke compared to low methylation levels (OR 5.10, 95% CI: 1.60-16.30).

In a rural population in northwest China, the hypomethylation status of ABCA1 and ABCG1 genes was strongly associated with the incidence of stroke. Significant correlations between CpG_19.20 methylation levels change in ABCG1 and stroke risk.