Association study of a functional catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and suicide attempts in patients with alcohol dependence

Nedić, Gordana; Nikolac, Matea; Nenadić Šviglin, Korona; Muck-Šeler, Dorotea; Borovečki, Fran; Pivac, Nela (2011) Association study of a functional catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and suicide attempts in patients with alcohol dependence. International journal of neuropsychopharmacology, 14 (3). pp. 377-388. ISSN 1461-1457

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Abstract

Alcohol dependence is frequently associated with aggressive and suicidal behavior. Genetic factors contribute to both behaviors. Candidate genes, related to suicide and aggression, include genes involved in serotonin, norepinephrine and dopamine pathways. The enzyme catechol-O-methyl transferase (COMT) degrades dopamine, epinephrine and norepinephrine. The functional polymorphism (COMT Val108/158Met) affects COMT activity, with the Valine (Val) variant associated with higher and the Methionine (Met) variant with lower COMT activity. This polymorphism is associated with aggressive and suicidal behavior, but the literature data on this relationship is contradictory and inconsistent. The hypothesis of this study was that Met allele carriers with alcohol dependence will have a higher frequency of suicide attempts compared to other genotypes. Participants were 312 male and 81 female medication-free patients with alcohol dependence and 487 male and 122 female unrelated, non-suicidal medication-free Caucasian healthy subjects. Our results showed significant (a 2 test with standardized residuals) differences in the frequencies of COMT variants in all alcoholics, alcoholics with different comorbid diagnoses, and in male but not in female alcoholics, with or without suicide attempts. Male alcoholic suicide attempters, compared to male non-attempters, had the higher frequency of Met/Met genotype or Met allele, and significantly (Kruskal Wallis ANOVA on Ranks and Mann Whitney test) higher aggression and depression scores. These results confirmed the associations between Met allele and aggressive behavior or violent suicide attempts in various psychiatric diagnoses, and suggested that Met allele of the COMT Val108/158Met might be used as an independent biomarker of suicidal behavior across different psychopathologies.

Item Type:

Article

Uncontrolled Keywords:

alcoholism; association study; COMT Val108/158Met polymorphism; suicide attempts

Subjects:

BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences

Divisions:

Division of Molecular Medicine

Projects:

Project title	Project leader	Project code	Project type
Genomic Analysis of Transcriptome and Interactome in Complex Disease Patients (Genomska analiza transkriptoma i interaktoma u bolesnika s kompleksnim bolestima)-	Fran Borovečki	108-1081874-1923	MZOS
Pharmacogenomics and proteomics of serotonergic and catecholaminergic system (Farmakogenomika i proteomika serotoninskog i kateholaminskog sustava)-	Dorotea Muck-Šeler	098-0982522-2457	MZOS
Molecular basis and treatment of psychiatric and stress related disorders (Molekularna podloga i liječenje psihijatrijskih i stresom izazvanih poremećaja)-	Nela Pivac	098-0982522-2455	MZOS