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Association of gene polymorphisms encoding dopaminergic system components and platelet MAO-B activity with alcohol dependence and alcohol dependence-related phenotypes

Nedić Erjavec, Gordana; Nenadić Sviglin, Korona; Nikolac Perković, Matea; Muck-Šeler, Dorotea; Jovanović, Tanja; Pivac, Nela (2014) Association of gene polymorphisms encoding dopaminergic system components and platelet MAO-B activity with alcohol dependence and alcohol dependence-related phenotypes. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 54 . pp. 321-327. ISSN 0278-5846

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Abstract

he present study aimed to evaluate the association of alcohol dependence and alcohol dependence-related phenotypes with platelet monoamine oxidase type B (MAO-B) activity, Val108/158Met of catechol-o-methyltransferase (COMT), variable number of tandem repeats (VNTR) in the third exon of dopamine receptor D4 (DRD4) gene, VNTR in the 3’-untranslated region of dopamine transporter (DAT) gene, -1021C/T of dopamine beta-hydroxylase (DBH) and MAO-B intron 13 polymorphisms. The study included 1270 Caucasian men and women of Croatian origin: 690 patients with alcohol dependence and 580 healthy controls. Patients with alcohol dependence were subdivided according to the presence or absence of withdrawal symptoms, aggressive behavior, severity of alcohol dependence, delirium tremens, comorbid depression, suicidal behavior, lifetime suicide attempt and early/late onset of alcohol abuse. The results, corrected for multiple testing, revealed increased platelet MAO-B activity in patients with alcohol dependence, subdivided into those with or without alcohol-related liver diseases, compared to control subjects (P < 0.001). In addition, we found an increased frequency of the COMT Met/Met genotype among suicidal (P = 0.002) and patients who attempted suicide (P < 0.001) and an increased frequency of COMT Val/Val genotype in patients with an early onset of alcohol dependence (P = 0.004). This study provides data from a sample of ethnically homogenous unrelated Caucasian subjects for future meta-analyses and suggests that the increased platelet MAO-B activity might be used as independent peripheral indicator of alcohol dependence, while COMT Val108/158Met polymorphism is associated with increased suicidality and early onset of alcohol dependence.

Item Type: Article
Uncontrolled Keywords: alcohol dependence; alcohol dependence-related phenotype; dopaminergic genes; pPlatelet MAO-B activity; polymorphisms
Subjects: BIOMEDICINE AND HEALTHCARE
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Neuroscience
Divisions: Division of Molecular Medicine
Projects:
Project titleProject leaderProject codeProject type
Molecular basis and treatment of psychiatric and stress related disorders (Molekularna podloga i liječenje psihijatrijskih i stresom izazvanih poremećaja)-Nela Pivac098-0982522-2455MZOS
Pharmacogenomics and proteomics of serotonergic and catecholaminergic system (Farmakogenomika i proteomika serotoninskog i kateholaminskog sustava)-Dorotea Muck-Šeler098-0982522-2457MZOS
Depositing User: Matea Nikolac Perković
Date Deposited: 01 Dec 2015 16:05
Last Modified: 01 Dec 2015 16:05
URI: http://fulir.irb.hr/id/eprint/2352
DOI: 10.1016/j.pnpbp.2014.07.002

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