Gene-gene interaction between MAOA and COMT in suicidal behavior: analysis in schizophrenia.
A large body of evidence suggests that suicidal behavior is associated with altered noradrenergic neurotransmission. Norepinephrine is degraded by monoamine oxidase A (MAOA) and catechol-O-methyl transferase (COMT). Our hypothesis is that the genes encoding MAOA and COMT might contain genetic variants conferring increased risk for suicidal behavior in schizophrenia and that both genes may interact each other. In order to test this hypothesis, we genotyped the promoter VNTR polymorphism in the MAOA gene and three COMT polymorphisms: -287A>G, Val/Met and 3'UTR C Ins/Del in a cohort of 270 schizophrenics in which 92 attempted suicide. No association between suicide attempt and the MAOA VNTR (P = 0.382), Val108/158Met (P = 0.788) or -287A>G (P = 0.420) polymorphisms was found, however, a slight significant finding was found for 3'UTR polymorphism (P = 0.050). Haplotype analysis for COMT gene revealed no association between suicide attempts and haplotype distribution (P = 0.451). As we tested for epistasis between MAOA VNTR and COMT Val/Met, we found no significant interaction in conferring risk for suicide attempts (P = 0.545). These results suggest that epistasis between MAOA and COMT genes may not influence suicidal behavior in patients with schizophrenia.
De Luca
Vincenzo
V
Neurogenetics Section, Clarke Site, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College Street R-30, Toronto, Ontario, Canada M5T 1R8. Vincenzo_Deluca@camh.net
Tharmalingam
Subi
S
Müller
Daniel J
DJ
Wong
Greg
G
de Bartolomeis
Andrea
A
Kennedy
James L
JL
D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D013406:Suicide, Attempted
D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase