Courtet Philippe, Jollant Fabrice, Buresi Catherine, Castelnau Didier, Mouthon Dominique, Malafosse Alain
Department of Psychological Medicine and Psychiatry, Lapeyronie Hospital, Montpellier Cedex, France.
Psychiatr Genet. 2005 Sep;15(3):189-93. doi: 10.1097/00041444-200509000-00009.
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.
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.
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.
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.
有力证据表明，血清素系统功能障碍与某些行为障碍有关，包括自杀行为和冲动性攻击。最近发现单胺氧化酶A基因（uVNTR）启动子区域存在功能多态性，且发现2 - 3等位基因的存在与较高水平的转录、中枢神经系统血清素反应性和冲动性攻击有关。该基因内含子2中的二核苷酸重复序列（单胺氧化酶A - CAn）先前已有描述，且与可变串联重复序列（VNTR）处于连锁不平衡状态。本研究的目的是在一个大样本中调查单胺氧化酶A基因是否与自杀行为易感性有关。
我们对738名有自杀未遂经历的西欧白种人和222名相同种族、无自杀行为史的对照者进行了基因分型。对单胺氧化酶A基因的两种变体进行了检测。
我们未发现单胺氧化酶A基因的两种变体与自杀行为之间存在任何关联。然而，通过暴力手段自杀的男性中uVNTR 2 - 3等位基因的频率显著高于采用非暴力手段自杀的男性。uVNTR 2 - 3等位基因与uVNTR 1 - 4等位基因的优势比为2.17 [95%置信区间（1.08 - 4.35）]。单倍型并未增强uVNTR所观察到的效应。
这些结果表明，单胺氧化酶A基因启动子高活性等位基因过多可能与使自杀行为倾向于暴力行为的特质有关。
