Global DNA methylation patterns in Alcohol Use Disorder

Schuch, Jaqueline B.; Bandeira, Cibele E.; Junior, Jorge L. S.; Müller, Diana; Charão, Mariele F.; Silva, Bruna S. da; Grevet, Eugenio H.; Kessler, Felix H. P.; von Diemen, Lisia; Rovaris, Diego L.; Bau, Claiton H. D.

doi:10.1590/1678-4685-GMB-2023-0139

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60 years of the PPGBM UFRGS - Special Issue • Genet. Mol. Biol. 46 (3 Suppl 1) • 2023 • https://doi.org/10.1590/1678-4685-GMB-2023-0139 copy

Global DNA methylation patterns in Alcohol Use Disorder

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Alcohol Use Disorder (AUD) is a highly prevalent condition worldwide that produces a wide range of pathophysiological consequences, with a critical impact on health and social issues. Alcohol influences gene expression through epigenetic changes mainly through DNA methylation. In this sense, levels of 5-methylcytosine (5-mC), namely Global DNA methylation (GMe), which can be influenced by environmental and hormonal effects, represent a putative biological mechanism underlying alcohol effects. Our aim was to investigate the influence of AUD diagnosis and alcohol patterns (i.e., years of addiction, use in the last 30 days, and alcohol severity) on GMe levels. The sample consisted of 256 men diagnosed with AUD and 361 men without AUD. DNA samples from peripheral blood were used to assess GMe levels, measured through the levels of 5-mC using high-performance liquid chromatography. Results from multiple linear regression analysis indicated that the presence of AUD was associated with lower GMe levels (beta=-0.155, p=0.011). Other alcohol-related outcomes were not associated with DNA methylation. Our findings are consistent with the hypothesis that the impact of chronic and heavy alcohol use in GMe could be a potential mechanism mediating the multiple organ damages related to AUD.

Keywords:
Substance use disorder; addiction; alcohol dependence; 5-methylcytosine

	AUD (n=256)	non-AUD (n=361)	Statistics	p-value
	Median [IQR]
Age (years)	49.0 [40-56]	29.0 [23-37]	U=14.89	<0.001
Schooling (years)	9.0 [6-12]	12.5 [11-15]	U=-11.81	<0.001
	Mean (SD)
GMe levels (%)	3.42 (0.48)	3.53 (0.41)	t=2.775	0.006
	n (%)
Skin color (white)	174 (68.0)	360 (99.7)	X²=127.01	<0.001
Marital status (married)	86 (34.0)	125 (34.6)	X²= 0.01	0.939
Nicotine use^a	200 (78.7)	94 (26.0)	X²=163.86	<0.001
Major depressive disorder^a	48 (24.9)	90 (24.9)	X²=0.01	0.999
Generalized anxiety disorder^a	10 (7.0)	19 (9.5)	X²=0.73	0.392
Bipolar disorder^a	23 (11.9)	21 (5.8)	X²=5.50	0.019

		GMe levels
	Median [IQR]	r Spearman	p-value
Age of first use (years)	15.0 [13-18]	0.053	0.524
Use in the last 30 days	29.5 [20-30]	0.084	0.314
Years of use	25.0 [14-33]	-0.004	0.961
Alcohol severity (ASI-06)	65 [60.5-70.5]	0.110	0.181
CIWA-Ar score	4.00 [1-6]	0.039	0.595
Standard drinks (daily)	25 [16.7-50]	0.021	0.765
Aspartate transaminase	37.0 [24.0-77.0]	0.021	0.768
Alanine transaminase	32.0 [20.0-56.7]	0.001	0.991
Gamma-glutamyl transferase	83.0 [39.7-160]	0.014	0.848

	Beta	t-Statistics	p-value
Alcohol Use Disorder	-0.155	-2.554	0.011
Sample origin^a	0.014	0.274	0.784
Age	0.007	0.136	0.892
Schooling	-0.034	-0.652	0.514
Skin-color	0.115	2.309	0.021
Nicotine use	-0.028	-0.563	0.573
Bipolar disorder	0.063	1.454	0.147

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[1] Send correspondence to
Claiton H. D. Bau. Universidade Federal do Rio Grande do Sul, Faculdade de Medicina, Departamento de Psiquiatria, Programa de Pós-Graduação em Psiquiatria e Ciências do Comportamento, R. Ramiro Barcelos, 2400, 90035-003, Santa Cecília, Porto Alegre, RS, Brazil. E-mail: claiton.bau@ufrgs.br.