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.
Highlights
Tobacco and alcohol are the most commonly used noxious compounds worldwide
When analysis was confined to patients who remained in hospital until days 3 or 7, no significant change in DNA methylation was detectable over time
We found no positive correlation with alcohol consumption on day 3, and no correlation with alcohol consumption or smoking on day 7
Summary
Tobacco and alcohol are the most commonly used noxious compounds worldwide. Cigarette smoking and alcoholism significantly increase the risk for a variety of medical and psychiatric conditions and different forms of cancer (Thun et al, 1997; Zaridze et al, 2009). As vitamin deficiency commonly occurs in alcoholdependent patients, alcohol-induced changes in DNA methylation and homocysteine might be explained by vitamin deficiencies (Cravo & Camilo, 2000; Heese et al, 2012). The vitamin status, and genetic variants may modify folate, vitamin B12 and homocysteine metabolism (Stover, 2011). Alcohol-induced changes of DNA methylation are possibly influenced by these genetic variants which are common in the general population. In a cohort of 363 patients with alcohol dependency, we analyzed changes of DNA methylation and attempted to identify parameters related to homocysteine metabolism which may mediate or modify the association of alcohol and DNA methylation, i.e. plasma levels of homocysteine and vitamins involved in homocysteine metabolism as well as genetic variants of homocysteine metabolism
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