Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder
João M. Castaldelli-Maia,
André Malbergier,
Adriana B. P. de Oliveira,
Ricardo A. Amaral,
André B. Negrão,
Priscila D. Gonçalves,
Antonio Ventriglio,
Domenico de Berardis,
Juliana de Antonio,
Isabela Firigato,
Gilka J. F. Gattás,
Fernanda de Toledo Gonçalves
Affiliations
João M. Castaldelli-Maia
Interdisciplinary Group of Studies on Alcohol and Drugs (GREA), Institute of Psychiatry, Medical School, Universidade de São Paulo, São Paulo 05403-903, Brazil
André Malbergier
Interdisciplinary Group of Studies on Alcohol and Drugs (GREA), Institute of Psychiatry, Medical School, Universidade de São Paulo, São Paulo 05403-903, Brazil
Adriana B. P. de Oliveira
Interdisciplinary Group of Studies on Alcohol and Drugs (GREA), Institute of Psychiatry, Medical School, Universidade de São Paulo, São Paulo 05403-903, Brazil
Ricardo A. Amaral
Interdisciplinary Group of Studies on Alcohol and Drugs (GREA), Institute of Psychiatry, Medical School, Universidade de São Paulo, São Paulo 05403-903, Brazil
André B. Negrão
Interdisciplinary Group of Studies on Alcohol and Drugs (GREA), Institute of Psychiatry, Medical School, Universidade de São Paulo, São Paulo 05403-903, Brazil
Priscila D. Gonçalves
Interdisciplinary Group of Studies on Alcohol and Drugs (GREA), Institute of Psychiatry, Medical School, Universidade de São Paulo, São Paulo 05403-903, Brazil
Antonio Ventriglio
Department of Experimental and Clinical Medicine, University of Foggia, 71122 Foggia, Italy
Domenico de Berardis
Department of Neurosciences and Imaging, University “G. D’Annunzio” Chieti, 66100 Chieti, Italy
Juliana de Antonio
Departamento de Medicina Legal e Ética Médica, Medicina Social e do Trabalho, Instituto Oscar Freire, LIM-40, Medical School, Universidade de São Paulo, São Paulo 05405-150, Brazil
Isabela Firigato
Departamento de Medicina Legal e Ética Médica, Medicina Social e do Trabalho, Instituto Oscar Freire, LIM-40, Medical School, Universidade de São Paulo, São Paulo 05405-150, Brazil
Gilka J. F. Gattás
Departamento de Medicina Legal e Ética Médica, Medicina Social e do Trabalho, Instituto Oscar Freire, LIM-40, Medical School, Universidade de São Paulo, São Paulo 05405-150, Brazil
Fernanda de Toledo Gonçalves
Departamento de Medicina Legal e Ética Médica, Medicina Social e do Trabalho, Instituto Oscar Freire, LIM-40, Medical School, Universidade de São Paulo, São Paulo 05405-150, Brazil
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.
