ALDH2 Polymorphism in Alcohol‐Related Cirrhosis Requiring Liver Transplantation: A Recipient–Donor Analysis

AIM: Genetic polymorphisms of alcohol-metabolizing enzymes influence drinking behavior and susceptibility to alcohol-related liver disease (ALD). This study aimed to clarify the distribution of ALDH2 and ADH1B genotypes in liver transplant recipients with ALD, and to explore associations with post-transplant drinking behavior using a recipient-donor paired design. METHODS: Twenty-four living donor liver transplant (LDLT) recipients with ALD, their corresponding living donors, and 50 healthy controls were analyzed. Single nucleotide polymorphisms of ALDH2 (rs671) and ADH1B (rs1229984) were determined by the Cycleave PCR method. Drinking behavior before and after transplantation was assessed by self-report and electronic health records. Post-transplant alcohol use was classified as habitual (≥ once per week) or occasional (< once per week). RESULTS: ALDH2 genotype distribution differed among three groups (p = 0.002), with enrichment of the ALDH2*1/*1 genotype in ALD recipients (92%). ADH1B genotype distribution also differed among groups (p = 0.041), although the effect size was modest. During a median follow-up of 5.3 years (range, 0.3-15.9 years), 11 recipients (45%) reported post-transplant alcohol use, including 5 habitual drinkers (20%). In an exploratory analysis, a non-significant trend toward higher rates of habitual drinking was observed among recipients who received grafts from donors with the ALDH2*1/*1 genotype compared with other genotypes (40% vs. 7%, p = 0.12). CONCLUSIONS: The ALDH2*1/*1 genotype was more prevalent among liver transplant recipients with alcohol-related cirrhosis than among donors or healthy controls, supporting a role of alcohol tolerance-related genetic background in progression to end-stage liver disease. Donor ALDH2 genotypes may also influence post-transplant drinking behavior in an exploratory manner.