title: Alcohol abuse and cigarette smoking are associated with global DNA hypermethylation: results from the German Investigation on Neurobiology in Alcoholism (GINA).
abstract: Recent studies have shown that smoking and alcoholism may be associated with altered DNA methylation and that alcohol consumption might induce changes in DNA methylation by altering homocysteine metabolism. In this monocenter study, we included 363 consecutive patients referred for hospitalization for alcohol detoxification treatment. Blood samples were obtained on treatment days 1, 3, and 7 for measurement of global DNA methylation in leukocytes by liquid chromatography tandem mass spectrometry. Genomic DNA was used for genotyping the following seven genetic variants of homocysteine metabolism: cystathionine beta-synthase (CBS) c.844_855ins68, dihydrofolate-reductase (DHFR) c.594 + 59del19bp, methylenetetrahydrofolate-reductase (MTHFR) c.677C > T and c.1298A > C, methyltetrahydrofolate-transferase (MTR) c.2756A > G, reduced folate carrier 1 (RFC1) c.80G > A, and transcobalamin 2 c.776C > G. Multivariate linear regression showed a positive correlation of global DNA methylation with alcohol consumption and smoking on day 1 of hospitalization. DNA methylation was not correlated with homocysteine or vitamin plasma levels, nor with the tested genetic variants of homocysteine metabolism. This suggests a direct effect of alcohol consumption and smoking on DNA methylation, which is not mediated by effects of alcohol on homocysteine metabolism.
authors.affiliation: University of Zurich, Department of Neurology, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Semmler
authors.affiliation: Department of Addiction and Psychotherapy, LVR-Clinic Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Heese
authors.affiliation: University of Bonn, Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital of Bonn, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Stoffel-Wagner
authors.affiliation: Center for Addiction Research, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hanover Medical School, Hanover, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Muschler
authors.affiliation: Center for Addiction Research, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hanover Medical School, Hanover, Germany.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Heberlein
authors.affiliation: University of Zurich, Institute of Organic Chemistry, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bigler
authors.affiliation: University of Zurich, Institute of Organic Chemistry, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Prost
authors.affiliation: Center for Addiction Research, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hanover Medical School, Hanover, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
authors.affiliation: Center for Addiction Research, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hanover Medical School, Hanover, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: Department of Addiction and Psychotherapy, LVR-Clinic Bonn, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Banger
authors.affiliation: Center for Addiction Research, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hanover Medical School, Hanover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
authors.affiliation: Center for Addiction Research, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hanover Medical School, Hanover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hillemacher
authors.affiliation: University of Zurich, Department of Neurology, Switzerland. Electronic address: michael.linnebank@usz.ch.
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebank
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics; D015331:Cohort Studies; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D014644:Genetic Variation / Q000502:physiology; D005858:Germany / Q000453:epidemiology; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics
chemical_list: D006710:Homocysteine
keywords: Alcohol; DNA methylation; Homocysteine; Single nucleotide polymorphism; Smoking; Vitamins