Opioid and Dopamine Genes Interact to Predict Naltrexone Response in a Randomized Alcohol Use Disorder Clinical Trial.

Autor: Anton RF; From the, Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, Charleston, South Carolina, USA., Voronin KE; From the, Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, Charleston, South Carolina, USA., Book SW; From the, Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, Charleston, South Carolina, USA., Latham PK; From the, Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, Charleston, South Carolina, USA., Randall PK; From the, Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, Charleston, South Carolina, USA., Glen WB; From the, Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, Charleston, South Carolina, USA., Hoffman M; From the, Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, Charleston, South Carolina, USA., Schacht JP; From the, Department of Psychiatry and Behavioral Sciences, Addiction Sciences Division, Medical University of South Carolina, Charleston, South Carolina, USA.
Jazyk: angličtina
Zdroj: Alcoholism, clinical and experimental research [Alcohol Clin Exp Res] 2020 Oct; Vol. 44 (10), pp. 2084-2096. Date of Electronic Publication: 2020 Sep 19.
DOI: 10.1111/acer.14431
Abstrakt: Background: While the opiate antagonist, naltrexone, is approved for treating alcohol use disorder (AUD), not everyone who receives the medication benefits from it. This study evaluated whether the OPRM1 SNP rs1799971 interacts with the dopamine transporter gene DAT1/SLC6A3 VNTR rs28363170 or the catechol-O-methyltransferase (COMT) gene SNP rs4680 in predicting naltrexone response.
Methods: Individuals who met DSM-IV alcohol dependence were randomly assigned to naltrexone (50 mg/d) or placebo based on their OPRM1 genotype (75 G-allele carriers and 77 A-allele homozygotes) and also genotyped for DAT1 VNTR (9 vs. 10 repeats) or COMT SNP (val/val vs. met carriers). Heavy drinking days (%HDD) were evaluated over 16 weeks and at the end of treatment. Effect sizes (d) for naltrexone response were calculated based on genotypes.
Results: Naltrexone, relative to placebo, significantly reduced %HDD among OPRM1 G carriers who also had DAT1 10/10 (p = 0.021, d = 0.72) or COMT val/val genotypes (p = 0.05, d = 0.80), and to a lesser degree in those OPRM1 A homozygotes who were also DAT1 9-repeat carriers (p = 0.09, d = 0.70) or COMT met carriers (p = 0.03, d = 0.63). All other genotype combinations showed no differential response to naltrexone. Diarrhea/abdominal pain was more prominent in OPRM1 A homozygotes who were also DAT 9 or COMT met carriers.
Conclusions: These results suggest that individuals with AUD with a more opioid-responsive genotype (OPRM1 G carriers) respond better to naltrexone if they have genotypes indicating normal/less dopamine tone (DAT1 10,10 or COMT val,val), while those with a less responsive opioid-responsive genotype (OPRM1 A homozygotes) respond better to naltrexone if they have genotypes indicating greater dopamine tone (DAT1 9-repeat or COMT met carriers). These results could lead to more personalized AUD treatments.
(© 2020 by the Research Society on Alcoholism.)
Databáze: MEDLINE
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