Combined analysis of the moderating effect of a GRIK1 polymorphism on the effects of topiramate for treating alcohol use disorder.
Alcohol use disorder
Heavy drinking
Pharmacogenetics
Pharmacotherapy
Precision medicine
Topiramate
Journal
Drug and alcohol dependence
ISSN: 1879-0046
Titre abrégé: Drug Alcohol Depend
Pays: Ireland
ID NLM: 7513587
Informations de publication
Date de publication:
01 08 2021
01 08 2021
Historique:
received:
03
02
2021
revised:
26
02
2021
accepted:
28
03
2021
pubmed:
29
5
2021
medline:
22
9
2021
entrez:
28
5
2021
Statut:
ppublish
Résumé
In an initial study, we reported that topiramate reduced heavy drinking among individuals who sought to reduce their drinking and that the effect was moderated by a single nucleotide polymorphism (SNP; rs2832407) in GRIK1, which encodes the kainate GluK1 receptor subunit (Kranzler et al., 2014). In a subsequent study that prospectively randomized patients to medication group based on their rs2832407 genotype, we replicated the main effect of topiramate but not the moderating effect of the SNP (Kranzler et al., 2021). Given the similar design of the two studies, here we combined the findings to provide greater statistical power to test the pharmacogenetic effect. This secondary analysis of two 12-week, randomized controlled trials of topiramate included a total of 292 European-ancestry individuals (67.1 % male; topiramate: 48.3 %, placebo: 51.7 %) with problematic alcohol use. Using MANOVA, we examined changes in self-reported alcohol consumption, problems resulting from alcohol use, and quality of life, and the biomarker γ-glutamyltransferase. To test the pharmacogenetic hypothesis, all patients were genotyped for rs2832407. There was a significant overall effect of topiramate on the alcohol-related outcomes (partial η Although topiramate is an efficacious medication for reducing drinking and alcohol-related problems among patients with problematic alcohol use, rs2832407 does not appear to moderate its therapeutic effects. www.clinicaltrials.gov registrations: NCT00626925 and NCT02371889.
Sections du résumé
BACKGROUND
In an initial study, we reported that topiramate reduced heavy drinking among individuals who sought to reduce their drinking and that the effect was moderated by a single nucleotide polymorphism (SNP; rs2832407) in GRIK1, which encodes the kainate GluK1 receptor subunit (Kranzler et al., 2014). In a subsequent study that prospectively randomized patients to medication group based on their rs2832407 genotype, we replicated the main effect of topiramate but not the moderating effect of the SNP (Kranzler et al., 2021). Given the similar design of the two studies, here we combined the findings to provide greater statistical power to test the pharmacogenetic effect.
MATERIAL AND METHODS
This secondary analysis of two 12-week, randomized controlled trials of topiramate included a total of 292 European-ancestry individuals (67.1 % male; topiramate: 48.3 %, placebo: 51.7 %) with problematic alcohol use. Using MANOVA, we examined changes in self-reported alcohol consumption, problems resulting from alcohol use, and quality of life, and the biomarker γ-glutamyltransferase. To test the pharmacogenetic hypothesis, all patients were genotyped for rs2832407.
RESULTS
There was a significant overall effect of topiramate on the alcohol-related outcomes (partial η
CONCLUSIONS
Although topiramate is an efficacious medication for reducing drinking and alcohol-related problems among patients with problematic alcohol use, rs2832407 does not appear to moderate its therapeutic effects. www.clinicaltrials.gov registrations: NCT00626925 and NCT02371889.
Identifiants
pubmed: 34049101
pii: S0376-8716(21)00257-X
doi: 10.1016/j.drugalcdep.2021.108762
pmc: PMC8282735
mid: NIHMS1707131
pii:
doi:
Substances chimiques
Topiramate
0H73WJJ391
Fructose
30237-26-4
Banques de données
ClinicalTrials.gov
['NCT00626925', 'NCT02371889']
Types de publication
Clinical Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
108762Subventions
Organisme : NIAAA NIH HHS
ID : P60 AA003510
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA023192
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA025539
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
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