title: Alcohol-induced changes in methylation status of individual CpG sites, and serum levels of vasopressin and atrial natriuretic peptide in alcohol-dependent patients during detoxification treatment.
abstract: Disturbances of volume-regulating peptides like vasopressin (AVP) and atrial natriuretic peptide (ANP) have been described in early abstinent alcohol-dependent patients. In a longitudinal approach, we investigated whether changes in AVP and ANP serum levels correlated to cytosine-phosphatidyl-guanine (CpG) methylation of the respective gene promoters on days 1, 7 and 14 of alcohol withdrawal. We analyzed the blood samples of 99 patients suffering from alcohol dependence alongside age- and BMI-matched controls. Concerning AVP promoter methylation, we observed an interaction between time of measurement and CpG loci with CpG 2 showing a significant increase in methylation from day 1 to 14. Serum levels of AVP were significantly decreased in the patient group. Compared to healthy controls, promoter-related DNA methylation of the ANP promoter was significantly reduced on days 7 and 14. Moreover, we detected a significant interaction between CpG position and group. In both cases the difference was mainly observed at CpG 1. The present study shows significant changes in the methylation status of individual CpG sites of AVP and ANP. Observing respective alterations of AVP serum protein levels in alcohol-dependent patients during detoxification treatment, we consider methylation as a possible mode of regulation for these proteins during alcohol detoxification.
authors.affiliation: Center for Addiction Research (CARe), Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Glahn
authors.forename: Rafael
authors.initials: R
authors.lastname: Riera Knorrenschild
authors.forename: Mathias
authors.initials: M
authors.lastname: Rhein
authors.forename: Mani
authors.initials: M
authors.lastname: Haschemi Nassab
authors.forename: Michael
authors.initials: M
authors.lastname: Gröschl
authors.forename: Annemarie
authors.initials: A
authors.lastname: Heberlein
authors.forename: Marc
authors.initials: M
authors.lastname: Muschler
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
authors.forename: Thomas
authors.initials: T
authors.lastname: Hillemacher
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000097:blood* / Q000235:genetics / Q000628:therapy*; D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000235:genetics*; D014667:Vasopressins / Q000097:blood* / Q000235:genetics; D055815:Young Adult
chemical_list: D014667:Vasopressins; D009320:Atrial Natriuretic Factor