Associations of global DNA methylation and homocysteine levels with abdominal aortic aneurysm: A cohort study from a population-based screening program in Sweden

Abdominal aortic aneurysm (AAA) is a life-threatening condition with a mortality rate of over 80%. Persistent smoking, which is a risk factor for AAA, has lasting effects on DNA methylation. Moreover, a plasma-amino acid, homocysteine, previously implicated in vascular diseases, including aneurysms, has well-established biological association with methylation. In the present study, we aimed to determine the global DNA methylation, homocysteine levels and their association with AAA and its growth. Enzyme-linked immunosorbent assay (ELISA) was used to quantify global DNA methylation in whole blood-DNA samples and diagnostic enzymatic assay quantified plasma homocysteine, from 65-year old men with (n = 116) and without AAA (n = 230) diagnosed at ultrasound screening. We found significantly higher global DNA methylation (p .001) and homocysteine levels (p .001) in men with AAA compared to those without AAA, and direct linear associations with baseline aortic diameter. On multivariable regression analysis, global DNA methylation (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and homocysteine levels (OR: 1.1; 95% CI:1.0-1.1) were positively associated with AAA, independent of smoking, medication use, and major co-morbidities. However, we did not find any significant association between DNA methylation or homocysteine levels with AAA growth during follow-up. We found that global DNA methylation and homocysteine levels are higher in men with AAA but are not associated with AAA growth. This indicates that different pathways and mechanisms may be involved in initiation and progression of AAA. More studies are needed to understand the precise role of DNA methylation, homocysteine and their interplay in AAA pathophysiology.