SLC6A3 gene methylation may be associated with alcohol use disorder, but personality and life stress may not influence methylation.

Background: DNA methylation plays a crucial role in gene regulation and has been implicated in various neuropsychiatric disorders, including alcohol use disorder (AUD). The rs27072 polymorphism within the SLC6A3 gene has been studied in addictive disorders; however, its role in epigenetic modifications remains unclear. This study investigates the methylation levels of CpG sites near rs27072 and their potential associations with AUD, personality traits, and environmental stressors.

Materials and methods: One hundred twenty-four male participants (66 patients with AUD and 58 controls) were analyzed for DNA methylation at CpG islands proximal to the rs27072 locus. The personality traits and life stress events were assessed in all participants.

Results: AUD patients had a lower methylation level than healthy controls (p = 0.003 for total average). However, the results changed to borderline significance after adjusting for clinical covariates in the analysis (p = 0.042), and the genotype at rs27072 did not modulate the methylation levels. There is high novelty seeking (p < 0.001), and more bad life events in patients with AUD than healthy controls (p < 0.001). Additionally, no significant correlations were found between methylation levels and personality traits or life stress scores (p > 0.05).

Conclusions: The methylation of the SLC6A3 gene may be marginally associated with AUD; however, the rs27072 genotype, personality, and life stress may not be directly linked to epigenetic modifications. Cross-sectional epigenetic studies may not establish causality; future studies with larger, more diverse cohorts and longitudinal designs are warranted to elucidate the complex interplay in AUD pathophysiology.