Epigenetic regulation and gene expression of vasopressin and atrial natriuretic peptide in alcohol withdrawal

Abstract

Disturbances of volume regulating peptides like vasopressin and atrial natriuretic peptide (ANP) have been described in early abstinent patients. Aim of the present study was to evaluate possible alterations of the promoter-related DNA methylation of the ANP and vasopressin precursor genes and the related mRNA-expression of these genes in early alcohol withdrawal. We analyzed blood samples of 57 healthy controls and of 111 patients suffering from alcohol dependence that were admitted for detoxification treatment. Promoter-related DNA methylation and mRNA-expression of vasopressin and ANP genes were assessed using real-time PCR. Vasopressin mRNA-expression was not statistically different between patients and controls. However, we found a significantly elevated promoter-related DNA methylation of the vasopressin gene in patients with alcohol dependence (Mann-Whitney U-test: Z=-2.178, p=0.029). ANP mRNA-expression was significantly elevated in alcoholic patients (Z=-6.240, p<0.001) while promoter-related DNA methylation of ANP was significantly decreased (Z=-2.282, p=0.023). Furthermore, promoter-related DNA methylation of ANP was significantly correlated to the extent of craving measured with the OCDS (r=-0.197, p=0.040). The findings of the present study show significant alterations of the mRNA-expression and promoter-related DNA methylation of vasopressin and especially ANP precursor genes in patients with alcohol dependence. Further studies focusing on longitudinal changes of epigenetic regulation and gene expression of both peptides are needed to clarify the pathophysiological role of these findings.