Abstract
Background: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.
Highlights
Alcohol use disorder (AUD) is a major public health problem [1,2]
The present study aims to investigate the possible association between polymorphisms in alcohol metabolizing enzymes (AME) polymorphism genes (ADH1B*2, ADH1B*3, ADH1C*1 and ALDH2*2) and the outcome of alcohol use disorder (AUD) treatment with naltrexone
Our findings support the use of naltrexone in those patients who might be less susceptible to alcohol dependence (i.e., ADH1C*1 and ALDH2*2), wherein these polymorphisms have been related to the AUD protection [6,10,11,12,32]
Summary
Alcohol use disorder (AUD) is a major public health problem [1,2]. It has been included among the top-ten risk factors for days of activity lost [3]. Alcohol metabolizing enzyme (AME) genes, alcohol dehydrogenases (ADH1B and ADH1C) and aldehyde dehydrogenase (ALDH2), are genetic factors associated with the AUD outcome [6,10,11,12]. The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. The outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. The association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
