Résumé
Compelling evidence suggests that serotonin system dysfunction is associated with certain behavioral disorders, including suicidal behavior and impulsive aggression. A functional polymorphism in the promoter region of the monoamine oxidase A gene (uVNTR) was recently identified and the presence of the 2-3 alleles was found to be associated with a higher level of transcription, central nervous system serotonergic responsivity and impulsive aggression. A dinucleotide repeat in intron 2 of the gene (monoamine oxidase A-CAn) has been described previously, and is in linkage disequilibrium with the variable number of tandom repeats (VNTR). The aim of the study was to investigate, in a large sample, whether the monoamine oxidase A gene was involved in the susceptibility to suicidal behavior.OBJECTIVECompelling evidence suggests that serotonin system dysfunction is associated with certain behavioral disorders, including suicidal behavior and impulsive aggression. A functional polymorphism in the promoter region of the monoamine oxidase A gene (uVNTR) was recently identified and the presence of the 2-3 alleles was found to be associated with a higher level of transcription, central nervous system serotonergic responsivity and impulsive aggression. A dinucleotide repeat in intron 2 of the gene (monoamine oxidase A-CAn) has been described previously, and is in linkage disequilibrium with the variable number of tandom repeats (VNTR). The aim of the study was to investigate, in a large sample, whether the monoamine oxidase A gene was involved in the susceptibility to suicidal behavior.We genotyped 738 West European Caucasians, who had made suicide attempts, and 222 controls of the same ethnic origin, with no history of suicidal behavior. The two variants of the monoamine oxidase A gene have been tested.METHODSWe genotyped 738 West European Caucasians, who had made suicide attempts, and 222 controls of the same ethnic origin, with no history of suicidal behavior. The two variants of the monoamine oxidase A gene have been tested.We did not find any association between the two monoamine oxidase A gene variants and suicidal behavior. However, the frequency of the uVNTR 2-3 alleles was significantly higher in men who had attempted suicide by violent means than in men who had used non-violent means. The odds ratio for the uVNTR 2-3 alleles versus the uVNTR 1-4 alleles was 2.17 [95% confidence interval (1.08-4.35)]. Haplotypes did not allow strengthening the effect observed with the uVNTR.RESULTSWe did not find any association between the two monoamine oxidase A gene variants and suicidal behavior. However, the frequency of the uVNTR 2-3 alleles was significantly higher in men who had attempted suicide by violent means than in men who had used non-violent means. The odds ratio for the uVNTR 2-3 alleles versus the uVNTR 1-4 alleles was 2.17 [95% confidence interval (1.08-4.35)]. Haplotypes did not allow strengthening the effect observed with the uVNTR.These results suggest that an excess of high-activity monoamine oxidase A gene promoter alleles may be associated with traits orienting suicidal behavior towards a violent act.CONCLUSIONThese results suggest that an excess of high-activity monoamine oxidase A gene promoter alleles may be associated with traits orienting suicidal behavior towards a violent act.