¹Taipei City Hospital, Songde Branch, Department of Addiction Sciences, Taipei City, Taiwan, ²School of Medicine, College of Medicine, Taipei Medical University, Department of Psychiatry, Taipei City, Taiwan

Background: Alcohol use disorder (AUD) is a complex psychiatric disorder, whose heritability is estimated to be around 50%. Of all, the respective impact of ADH1B rs1229984 and ALDH2 rs671 on drinking habits or prognosis is widely reported. More than 90% of Han Chinese in Taiwan carry at least one fast-metabolizing T allele at ADH1B rs1229984, while approximately 50% carry at least one slow-metabolizing A allele at ALDH2 rs671. Both T allele at ADH1B rs1229984 and A allele at ALDH2 rs671 are associated with reduced risk of AUD. However, the interactive effects between ADH1B and ALDH2 on the drinking outcome after naltrexone treatments are not elucidated in previous studies.

Aims & Objectives: To investigate the individual and interactive effects of ADH1B (rs1229984 T/C) and ALDH2 (rs671 G/A) polymorphisms on drinking outcomes following 12 weeks of naltrexone treatment in patients with AUD.

Method: Patients with AUD who received 12 weeks of naltrexone treatment (up to 50 mg/day) were genotyped. Assessments of drinking outcomes (drinking days per week, heavy drinking days per week, drinks per drinking day, abstinence days per week, max drinks per day, Visual Analogue Score for Craving, and Penn Alcohol Craving Scale) and psychological outcomes (Beck Depression Inventory and Beck Anxiety Inventory) were conducted at baseline and at weeks 4, 8, and 12. Generalized Estimation Equations were used to analyze the group effect, time effect, and the interaction effect of naltrexone on drinking and psychological outcomes over time between different genotypes.

Results: A total of 212 patients were enrolled and divided into 4 groups, including 66 patients with TT/GG genotype, 120 patients with CT/GG or CC/GG genotypes, 8 patients with TT/AG genotype, and 18 patients with CT/AG or CC/AG genotypes. All groups showed significant reductions in drinking days, heavy drinking days, drinks per drinking day, craving, and depressive and anxiety symptoms over 12 weeks (time effect p < 0.01 in all outcomes). No significant group-by-time interaction was observed. Although the TT/AG group (fast ethanol metabolizer ADH1B T/T and slow acetaldehyde metabolizer ALDH2 A/G) has more drinks per drinking day (group effect p = 0.03) and more drinking days per week (group effect p = 0.048), despite drinking later in life than other groups.

Discussion & Conclusions: In this cohort of treatment-seeking AUD patients, ALDH2 and ADH1B polymorphisms did not significantly modify treatment responses. However, patients with a certain genotype combination, specifically fast ethanol metabolizer ADH1B T/T and slow acetaldehyde metabolizer ALDH2 A/G, may need individualized interventions due to possibly greater drinking severity.