Association and Interaction of the MAOA Promoter uVNTR Polymorphism with Suicide Attempts in Patients with Major Depressive Disorder

Background: This study aimed to explore the association between alleles of the MAOA uVNTR polymorphism and patients with major depressive disorder (MDD) who had attempted suicide, using multiple controls. The symptom profiles and personal characteristics in each group were also compared. Methods: Four different groups was included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide from emergency room in a general hospital, and 109 patients with MDD who had attempted suicide. Results: An intergroup difference in allelic frequency was found between female suicidal subjects from the community and female suicidal subjects with MDD (P = 0.028): heterozygosity for the long-form variant of the MAOA polymorphism (≧ 3.5 repeats) was found to be a potential protective factor against MDD among female suicidal subjects (OR = 0.396). By multivariate logistic regression analysis, the long-form variant was found to be associated with suicide after controlling for the effect of gender (P = 0.004). An interaction was also found between depression and suicide that showed a negative correlation with the MAOA long-form variant (P = 0.045, OR = 0.503). Structural equation modeling showed, neuroticism, extraversion, low levels of anxiety, high levels of depressive symptoms, and smoking were associated with suicidal behavior in MDD group, not in the group of subjects without MDD. Conclusion: The MAOA long-form variant was associated with enhanced vulnerability to suicide in the general population. Depressive symptoms and smoking were associated with suicide attempts, whereas anxiety was a protective factor against suicidal behavior in participants with MDD. Furthermore, we found that the MAOA longand short-form variants had different effects in controls and in patients with MDD, and the reverse effect of the long-form MAOA variant on MDD patients who had attempted suicide was revealed only by analysis of interactions. The results