Alcoholism: Genetic Markers Determined For Abstinence Duration

Victor M. Karpyak, M.D., Ph.D.  Medical Director, Intensive Addiction Treatment Program Director, Mayo Clinic Addiction Services Consultant, Department of Psychiatry and Psychology  Assistant Professor of Psychiatry Mayo Clinic College of Medicine MedicalResearch.com Interview with:
Victor M. Karpyak, M.D., Ph.D. 

Medical Director, Intensive Addiction Treatment Program
Director, Mayo Clinic Addiction Services
Consultant, Department of Psychiatry and Psychology
Assistant Professor of Psychiatry  Mayo Clinic College of Medicine

Medical Research: What is the background for this study?

Dr. Karpyak: The staggering costs of alcohol use disorders call for the development and implementation of evidence-based treatment strategies. Several medications (acamprosate, naltrexone, and disulfiram) were approved for treatment of alcohol use disorders; yet, only a fraction of patients respond to each medication. Clearly, response predictors are needed to improve treatment efficacy and personalize recommendations for treatment selection. It is expected that pharmacogenomic research will aid the discovery of such predictors.

Medical Research: What are the main findings?

Dr. Karpyak: Study was conducted in the discovery sample of alcohol-dependent subjects treated with acamprosate in community-based treatment programs in the United States. Data from alcohol-dependent subjects treated with acamprosate in the German study PREDICT were used for replication of the top association findings. In the discovery sample, shorter abstinence was associated with increased intensity of alcohol craving and lower number of days between the last drink and initiation of acamprosate treatment. After adjustment for these covariates, length of abstinence was significantly (P = 4.6 × 10 − 5) associated with rs2058878 variant in GRIN2B gene. In the replication sample, shorter abstinence was associated with increased craving, increased depressive mood score and higher alcohol consumption. Association of abstinence length with GRIN2B rs2058878 was marginally significant (P = 0.0675); as in the discovery sample, the minor A allele was associated with longer abstinence. Furthermore, rs2300272, which is in strong linkage disequilibrium with rs2058878, was also associated with abstinence length (P = 0.049). This is the first report of a replicated association of genetic markers with the length of abstinence in acamprosate-treated alcoholics.

Medical Research: What should clinicians and patients take away from your report?

Dr. Karpyak: Our findings indicate that genetic variation, and specifically rs2058878 and rs2300272 variants in GRIN2B gene are associated with abstinence length during acamprosate treatment. These findings support experimental evidence implicating NMDA receptors in the treatment effects of acamprosate. Our findings also indicate the need to account for clinical factors, including intensity of alcohol craving, depressed mood and the number of days since last drink, when considering initiation of acamprosate treatment.

Our findings are based on the data collected from patients treated in community based programs and, therefore, should be relevant and translatable to treatment of patients with alcohol use disorders treated in similar programs.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Karpyak: Future studies need to investigate the potential role of variations identified in our study as potential biomarkers of abstinence length in treatment-seeking alcoholics and determine the physiological and molecular mechanisms underlying these association findings. It is also important to investigate the difference in drug-related and non-related mechanisms contributing to sobriety.

Citation:

Genetic markers associated with abstinence length in alcohol-dependent subjects treated with acamprosate
Karpyak VM1, Biernacka JM2, Geske JR3, Jenkins GD3, Cunningham JM4, Rüegg J5, Kononenko O6, Leontovich AA3, Abulseoud OA1, Hall-Flavin DK1, Loukianova LL1, Schneekloth TD1, Skime MK1, Frank J7, Nöthen MM8, Rietschel M7, Kiefer F9, Mann KF9, Weinshilboum RM10, Frye MA1, Choi DS11.

Transl Psychiatry. 2014 Oct 7;4:e462. doi: 10.1038/tp.2014.103.

 

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