Combination of DAT and DBH gene polymorphisms with a family history of alcohol use disorders increases the risk of withdrawal seizures and delirium tremens during alcohol withdrawal in alcohol-dependent men

Kibitov A.O.; Ivashchenko D.V.; Brodianskiĭ V.M.; Chuprova N.A.; Shuvalov S.A.

doi:https://doi.org/10.17116/jnevro201611612168-80

Kibitov A.O.

Laboratoriia molekuliarnoĭ genetiki Natsional'nogo nauchnogo tsentra narkologii, Moskva

Ivashchenko D.V.

Bekhterev St. Petersburg Psychoneurological Research Institute, St. Petersburg

Brodianskiĭ V.M.

Laboratoriia molekuliarnoĭ genetiki Natsional'nogo nauchnogo tsentra narkologii, Moskva

Chuprova N.A.

Laboratoriia molekuliarnoĭ genetiki Natsional'nogo nauchnogo tsentra narkologii, Moskva

Shuvalov S.A.

Natsional'nyĭ nauchnyĭ tsentr narkologii, Moskva

Combination of DAT and DBH gene polymorphisms with a family history of alcohol use disorders increases the risk of withdrawal seizures and delirium tremens during alcohol withdrawal in alcohol-dependent men

Authors:

Kibitov A.O., Ivashchenko D.V., Brodianskiĭ V.M., Chuprova N.A., Shuvalov S.A.

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Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(12): 68‑80

DOI: 10.17116/jnevro201611612168-80

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To cite this article:

Kibitov AO, Ivashchenko DV, Brodianskiĭ VM, Chuprova NA, Shuvalov SA. Combination of DAT and DBH gene polymorphisms with a family history of alcohol use disorders increases the risk of withdrawal seizures and delirium tremens during alcohol withdrawal in alcohol-dependent men. S.S. Korsakov Journal of Neurology and Psychiatry. 2016;116(12):68‑80. (In Russ.)
https://doi.org/10.17116/jnevro201611612168-80

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

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Abstract:

Objective. To explore the genetic influence of a family history of alcohol use disorders and the dopamine transporter SLC6A3 (DAT1) and dopamine beta-hydroxylase (DBH) gene polymorphisms on the risk of severe complications (withdrawal seizures (AWS) and delirium tremens (DT)) during alcohol withdrawal in alcohol-dependent men. Material and methods. We investigated the effects of 3 previously reported candidate genetic variations: 40-bp variable number tandem repeat (VNTR) polymorphism and C/T exon 15 (rs27072) in the 3’ untranslated region (3’ UTR) of the SLC6A3(DAT1) gene, and –1021 C/T (rs1611115) of DBH gene in 266 alcohol-dependent Russian male inpatients in two groups by presence (SC group: AWS, DT, AWS+DT, n=130) or absence (n=136) of severe complications diagnosed by ICD-10 during current alcohol withdrawal. Clinically important information and a family history of alcohol use disorders (FH) were obtained by semi-structured interview. Results. Patients in SC group more often have positive FH (54.6% vs. 33%, p=0.001) and their age at first alcohol use (FAU) was lower (16±3.53y.o vs. 17±1.66 y.o, p=0.001). Logistic regression revealed that FH predicts severe complications in total (р=0.001) and DT (р=0.003), FAU independently predicts severe complications in total (р=0.008), AWS (р=0.04), DT (р=0.032), AWS+DT (р=0.048) and every year of delay alcohol use decreases the risk by 18—30%. The gene polymorphisms interact with FAU to decrease the FAU influence on the risk of AWS (T variant of DAT (rs27072), р=0.04), (AWS+DT) and DT (T variant of DBH (rs1611115), р=0.023 and р=0.06). The T variant of DAT (rs27072) is associated with FAU (p=0.007) and increases the risk of (AWS+DT) (р=0.036), but decreases the risk of AWS (р=0.038) and of DT (р=0.021) too, but only in interaction with positive FH. The 9 repeat variant (9R) of DAT VNTR is associated with AWS (p=0.009), but the risk of AWS (р=0.004) and of SC in total (р=0.001) are elevated only in 9R carriers with positive FH. The 9R independently increases the risk of DT (р=0.048) and the effect become more robust in 9R carriers with high density of FH (р=0.014). The gene x gene interaction decreases the risk of DT (р=0.055). According to an analysis of total cohort of patients, the T variant of DBH (rs1611115) is associated with any kind of manifestation of delirium in alcohol-dependent men (p=0.039). Conclusion. This study demonstrate the genetic influence of a family history of alcohol use disorders and DAT and DBH gene polymorphisms on the risk of withdrawal seizures and delirium tremens. The interaction of genetic variations with positive family history provides the most robust effect, the interaction of genetic variations with the age at first alcohol use may «protect» their carriers from negative influence of this «behavioral» risk factor. Replication in large cohorts of patients is necessary to verify these findings for subsequent use in prevention programs.

Keywords:

alcohol dependence

alcohol withdrawal

withdrawal seizures

delirium tremens

genetics

heredity

family history

genetic polymorphisms

dopamine

dopamine transporter

dopamine beta-hydroxylase

Authors:

Kibitov A.O.

Laboratoriia molekuliarnoĭ genetiki Natsional'nogo nauchnogo tsentra narkologii, Moskva

Ivashchenko D.V.

Bekhterev St. Petersburg Psychoneurological Research Institute, St. Petersburg

Brodianskiĭ V.M.

Laboratoriia molekuliarnoĭ genetiki Natsional'nogo nauchnogo tsentra narkologii, Moskva

Chuprova N.A.

Laboratoriia molekuliarnoĭ genetiki Natsional'nogo nauchnogo tsentra narkologii, Moskva

Shuvalov S.A.

Natsional'nyĭ nauchnyĭ tsentr narkologii, Moskva

Close metadata

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