title: Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study.
abstract: The available data from preclinical and pharmacological studies on the role of the C-O-methyl transferase (COMT) support the hypothesis that abnormal catecholamine transmission has been implicated in the pathogenesis of mood disorders (MD). We examined the relationship of a common functional polymorphism (Val108/158Met) in the COMT gene, which accounts for four-fold variation in enzyme activity, with 'early-onset' (EO) forms (less than or equal to 25 years) of MD, including patients with major depressive disorder (EO-MDD) and bipolar patients (EO-BPD), in a European multicenter case-control sample. Our sample includes 378 MDD (120 EO-MDD), 506 BPD (222 EO-BPD) and 628 controls. An association was found between the high-activity COMT Val allele, particularly the COMT Val/Val genotype and EO-MDD. These findings suggest that the COMT Val/Val genotype may be involved in EO-MDD or may be in linkage disequilibrium with a different causative polymorphism in the vicinity. The COMT gene may have complex and pleiotropic effects on susceptibility and symptomatology of neuropsychiatric disorders.
authors.affiliation: Department of Psychiatry, University Clinics of Brussels, Erasme Hospital, Free University of Brussels, Belgium. imassat@ulb.ac.be
authors.forename: I
authors.initials: I
authors.lastname: Massat
authors.forename: D
authors.initials: D
authors.lastname: Souery
authors.forename: J
authors.initials: J
authors.lastname: Del-Favero
authors.forename: M
authors.initials: M
authors.lastname: Nothen
authors.forename: D
authors.initials: D
authors.lastname: Blackwood
authors.forename: W
authors.initials: W
authors.lastname: Muir
authors.forename: R
authors.initials: R
authors.lastname: Kaneva
authors.forename: A
authors.initials: A
authors.lastname: Serretti
authors.forename: C
authors.initials: C
authors.lastname: Lorenzi
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: V
authors.initials: V
authors.lastname: Milanova
authors.forename: G N
authors.initials: GN
authors.lastname: Papadimitriou
authors.forename: D
authors.initials: D
authors.lastname: Dikeos
authors.forename: C
authors.initials: C
authors.lastname: Van Broekhoven
authors.forename: J
authors.initials: J
authors.lastname: Mendlewicz
mesh_terms: D000367:Age Factors; D019943:Amino Acid Substitution / Q000235:genetics; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003865:Major Depressive Disorder / Q000201:enzymology / Q000235:genetics*; D005060:Europe; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012016:Reference Values; D012307:Risk Factors
chemical_list: D002394:Catechol O-Methyltransferase