Gene-gene interaction between MAOA and COMT in suicidal behavior.
Several lines of evidence suggest that suicidal behavior is associated with altered noradrenergic neurotransmission. Noradrenaline (NA) is catabolized by monoamine oxidase A (MAOA) and cathecol-O-methyl transferase (COMT). We hypothesized that the genes encoding MAOA and COMT might contain genetic variation conferring increased risk for attempted suicide. In order to test this hypothesis, we genotyped the 941T > G and the promoter VNTR polymorphisms in the MAOA gene and the Val 108/158 Met COMT polymorphism in 305 families with at least one member having bipolar disorder (BD). No association with history of suicide attempt was found either in the MAOA polymorphisms (VNTR:LRS = 1.90, d.f. = 1, p = 0.16; 941T > G:LRS = 1.39, d.f. = 1, p = 0.23), or with the Val 158 Met polymorphism (LRS = 1.61, d.f.=1, p = 0.20). When we performed the haplotype analysis for MAOA gene, we found no association between suicide attempt and haplotype distribution (LRS = 3.07, d.f. = 2, p = 0.21). As both genes are involved in degrading noradreanline, we also tested the hypothesis of epistasis between MAOA polymorphisms and Val158Met, however, no additive effect was found in conferring risk for suicide attempt. These findings suggest that MAOA and COMT genes may not influence suicidal behavior in patients with bipolar disorder.
De Luca
Vincenzo
V
Neurogenetics Section, Clarke Site, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Ont., Canada. Vincenzo_Deluca@camh.net
Tharmalingam
Subi
S
Sicard
Tricia
T
Kennedy
James L
JL
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000150:complications / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D016009:Chi-Square Distribution; D005192:Family Health; D005260:Female; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D008995:Monoamine Oxidase / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D012306:Risk; D013406:Suicide, Attempted; D014633:Valine / Q000235:genetics
D008715:Methionine; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; D014633:Valine