Epigenome-wide association study identifies novel genes associated with ischemic stroke

Area of Science:

• Genetics
• Epigenetics
• Cardiovascular Disease

Background:

• DNA methylation alterations are implicated in ischemic stroke pathogenesis.
• Specific genes and their functional roles in ischemic stroke require further elucidation.
• This study focuses on identifying differentially methylated genes in a Chinese population.

Purpose of the Study:

• To identify genes with differential DNA methylation in Chinese ischemic stroke patients.
• To investigate the functional relevance of these genes in stroke development.
• To validate findings in independent Chinese and European cohorts.

Main Methods:

• Genome-wide DNA methylation analysis using Illumina Methylation EPIC Array in a discovery cohort.
• Targeted bisulfite sequencing for validation in a larger Chinese cohort.
• Verification of key findings in an external European cohort.
• In vitro experiments using engineered human umbilical vein endothelial cells.

Main Results:

• Six CpG loci (TRIM6, FLRT2, SOX1, SOX17, AGBL4, FAM84A) showed increased DNA methylation, and one locus (TLN2) showed decreased methylation in ischemic stroke cases.
• Six differentially methylated probes were confirmed in an independent Chinese population.
• One probe at TRIM6 was validated in a European cohort.
• Methylation changes at TRIM6, TLN2, and FLRT2 were associated with endothelial cell adhesion and atherosclerosis in vitro.

Conclusions:

• Altered DNA methylation of TRIM6, TLN2, and FLRT2 genes is associated with ischemic stroke in Chinese populations.
• These epigenetic modifications may play a functional role in the development of ischemic stroke.
• The findings highlight potential therapeutic targets for ischemic stroke prevention and treatment.