title: Association of gene polymorphisms encoding dopaminergic system components and platelet MAO-B activity with alcohol dependence and alcohol dependence-related phenotypes.
abstract: The 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 homogeneous 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.
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Nedic Erjavec
authors.affiliation: Center for Alcoholism and Other Addictions, Psychiatric Hospital Vrapce, Zagreb, Croatia.
authors.forename: Korona
authors.initials: K
authors.lastname: Nenadic Sviglin
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
authors.forename: Matea
authors.initials: M
authors.lastname: Nikolac Perkovic
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
authors.forename: Dorotea
authors.initials: D
authors.lastname: Muck-Seler
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
authors.affiliation: Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia. Electronic address: npivac@irb.hr.
authors.forename: Nela
authors.initials: N
authors.lastname: Pivac
mesh_terms: D000328:Adult; D017668:Age of Onset; D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000097:blood*; D010641:Phenotype; D011110:Polymorphism, Genetic; D013405:Suicide; D044465:White People / Q000235:genetics
chemical_list: D008995:Monoamine Oxidase; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Alcohol dependence; Alcohol dependence-related phenotype; Dopaminergic genes; Platelet MAO-B activity; Polymorphisms