DNA Methylation Analysis of the Angiotensin Converting Enzyme (ACE) Gene in Major Depression

Abstract

BackgroundThe angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ∼40%–50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood.Materials and MethodsThe main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls.ResultsWe detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04).ConclusionThe results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders.

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

“…The same result was supported in Chinese population where it was reported that ACE gene polymorphism did not affect response to the treatment 13 . Also, Zill et al suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD 40 . Depression were also significantly associated with an increase in cortisol secretion and, it is stated that ACE gene rs4295, rs4311, rs4343, rs4291, rs4333 and rs4351 variations influence cortisol secretion 41 .…”

“…Also, MDD is because of a complex genetic heterogeneity. Recent studies have shown that different genetic variants may contribute to the development of the MDD such as ACE gene polymorphism [4][5][6][7] .…”

Complex Treatment of Erectile Dysfunction with Vascular Factor Deficit by Use of Pluripotent Fetal Stem Cells

“…As the transcription of ACE is strongly associated with the levels of DNA methylation presenting at its promoter [25], aberrant expression of this gene might also lead to the erectile associated dysfunction. In addition, since DNA methyltransferases (DNMTs) as well as other histone modifiers deposit and maintain DNA methylation [26,27], ectopic levels of epigenetic modifiers might also cause erectile dysfunction.…”

Biology of Stress and Physical Performance

“…Angiotensinconverting enzyme (ACE) has been one of the main molecular markers associated with physical performance in humans, especially insertion/deletion polymorphism; in recent studies it has been associated with hyperactivity of the HPA axis and increased secretion of cortisol in patients under stress [28,29]. The presence of this polymorphism has been recently implicated with various behavioral disorders and increased mortality in patients with cardiovascular disease who present with depression [28,30]. The proposed model for neuroendocrine regulation of the HPA axis is observed in Figure 1. …”