Methylation in the Promoter Region of the Dopamine Transporter DAT1 Gene in People Addicted to Nicotine

Jolanta Chmielowiec; Krzysztof Chmielowiec; Aleksandra Strońska-Pluta; Aleksandra Suchanecka; Kinga Humińska-Lisowska; Milena Lachowicz; Marta Niewczas; Monika Białecka; Małgorzata Śmiarowska; Anna Grzywacz

doi:10.3390/ijerph19148602

Methylation in the Promoter Region of the Dopamine Transporter DAT1 Gene in People Addicted to Nicotine

Int J Environ Res Public Health. 2022 Jul 14;19(14):8602. doi: 10.3390/ijerph19148602.

Affiliations

¹ Department of Hygiene and Epidemiology, Collegium Medicum, University of Zielona Góra, 65-046 Zielona Gora, Poland.
² Independent Laboratory of Health Promotion, Pomeranian Medical University in Szczecin, 70-204 Szczecin, Poland.
³ Faculty of Physical Education, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland.
⁴ Department of Psychology, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland.
⁵ Faculty of Physical Education, University of Rzeszow, 35-959 Rzeszow, Poland.
⁶ Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University, 70-111 Szczecin, Poland.

Abstract

The dopaminergic system is a crucial element of the addiction processes. The dopamine transporter modulates the dynamics and levels of released dopamine in the synaptic cleft. Therefore, regulation of dopamine transporter (DAT1) gene expression is critical for maintaining homeostasis in the dopaminergic system. The aim of our study is evaluation of the methylation status of 33 CpG islands located in the DAT1 gene promoter region related to nicotine dependency. We investigated 142 nicotine-dependent subjects and 238 controls. Our results show that as many as 14 of the 33 CpG islands tested had statistically significantly higher methylation in the nicotine-dependent group compared to the control group. After applying Bonferroni correction, the total number of methylation sites was also significantly higher in the dependent subjects group. The analysis of the methylation status of particular CpG sites revealed a new direction of research regarding the biological aspects of nicotine addiction.

Keywords: DAT1 gene; nicotine addiction; promoter methylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CpG Islands
DNA Methylation
Dopamine Plasma Membrane Transport Proteins* / genetics
Humans
Nicotine
Promoter Regions, Genetic
Tobacco Use Disorder* / genetics

Substances

Dopamine Plasma Membrane Transport Proteins
Nicotine

Grants and funding

The project is financed by the program of the Minister of Science and Higher Education under the name “Regional Initiative of Excellence” in 2019–2022, project number 002/RID/2018/19, at an amount of 12,000,000 PLN.