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

Abstract

Alcohol dependence is frequently associated with aggressive and suicidal behaviour. Genetic factors contribute to both behaviours. 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 behaviour, 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 (χ2 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 behaviour or violent suicide attempts in various psychiatric diagnoses, and suggested that Met allele of the COMT Val108/158 Met might be used as an independent biomarker of suicidal behaviour across different psychopathologies.

No association between COMT val158met polymorphism and suicidal behavior: meta-analysis and new data

“…With regard to the literature search, a total of 18 papers were identified, but only 12 were included in this meta-analysis, including our case-control study [1,5,29,33-40] (Table 1). The six excluded studies did not comply with the inclusion criteria: in two of these studies genotype frequencies could not be obtained [24,25]; other study was carried out in families [41]; in other report the sample overlapped with a previous one [26]; the fifth was a meta-analysis [11], and the sixth a review [42].…”

Genetics of Aggression

“…(109). The Met/Met genotype has lower enzyme activity and is associated with higher levels of aggression and incidence of suicide attempts in schizophrenics and alcoholics (80,85). These studies should be viewed with caution, however, because of the small sample sizes, differences in gender, patient history, environmental conditions, and heterogeneity of psychiatric manifestations.…”

Polymorphisms of COMTVal158Metand DAT13′-UTR VNTRin Illicit Drug Use and Drug-Related Psychiatric Disorders

“…Although the regulatory role of genes in metabolism/signaling involved in the pathogenesis of depression (Opmeer, Kortekaas, & Aleman, 2010) and suicide behaviors (Tovilla-Zarate et al, 2011) has been reported, studies of its role in substance users are still lacking. To the best of our knowledge, only (Nedic et al, 2011) has reported that the Met allele of COMT Val108/158 Met is a potential biomarker of suicidal behavior among patients with alcohol dependence. This study revealed no involvement of the COMT and DAT1 gene variants in the pathogenesis of DIM and suicide attempts among illicit drug users.…”