PB0373 - "Understanding the etiopathology of Venous thromboembolism (VTE) by examining altered Mitochondrial DNA methylation pattern"

Background: Mitochondria are the key energetic site of the cell and also execute a vital role in many cellular processes. Mitochondrial DNA methylation considered as one of the foremost epigenetic modifications which plays a significant role in the pathophysiology of numerous cardiovascular conditions, including coronary artery disease, atherosclerosis, stroke etc. Perturbed mitochondrial DNA methylation could contribute as one of the confounding factors in Venous Thromboembolism (VTE) pathogenesis.

Aims: Investigation of methylation pattern of mitochondrial genes in high-altitude VTE (HA-VTE) and sea-level VTE (SL-VTE) to understand its role in disease development.

Methods: The study participants were patients from Indian Army command hospitals. DNA was extracted from peripheral blood and sequencing was done. DNA methylation profiles of mitochondrial genes from HA-VTE and SL-VTE were obtained. Methylation differences were analysed along with gene-gene and protein-protein interaction studies.

Results: Significant differential methylation was observed between HA-VTE and SL-VTE study groups showed 120 hypermethylated genes and 138 hypomethylated genes. On the basis of the region of occurrences, hypermethylated and hypomethylated genes were localized on promoter region, intronic region, exon region, 3ˈ-UTR, 5ˈ-UTR, Transcription termination site (TTS), non-coding and intergenic region respectively and percentage of methylation differences (>10% cut off) were evaluated as mentioned in table. TCA cycle and NADH dehydrogenase emerged as highly enriched pathways in gene-gene interaction while L-2-hydroxyglutaric acid pathway on protein -protein interaction.

Conclusion(s): These findings underscore the significant involvement of mitochondrial DNA methylation in the pathophysiology of thrombosis, emphasizing the promising avenue for investigating the role of mitochondria in thrombotic processes.