NOS-I and -III Gene Variants are Differentially Associated With Facets of Suicidal Behavior and Aggression-Related Traits

Nitric oxide (NO) is a neurotransmitter which modulates depressive and aggressive behaviors. We studied gene variants of NOS-I (rs2682826;rs1353939;rs2293049;rs693534) and NOS-III (rs2070744;rs1799983;rs891512) in a total of 571 cases (167 German suicide attempters, 92 Caucasian suicide completers and 312 German healthy subjects). A NOS-I risk haplotype C-G-G (rs2682826-rs1353939-rs693534) was associated with suicidal behavior (P = 0.01), and more specifically with suicide attempts (P = 0.01). Sliding windows analysis showed similar results for the haplotype G-G (rs1353939-rs693534) being a risk factor for suicidal behavior (P = 0.01) again especially in suicide attempters (P = 0.004). Additionally, the G-allele of rs693534 was associated with suicidal behavior (P = 0.005) and more specifically with suicide attempts (P = 0.003). Interestingly, the same haplotype (G-G) as well as the rs693534 G-allele were also associated with increased aggression. Regarding NOS-III, a protective haplotype C-T-A (rs2070744-rs1799983-rs891512) was observed (P = 0.01) with a pronounced effect against suicide completion (P = 0.005). Sliding window analysis showed the same effect of haplotype T-A (rs1799983-rs891512) (P = 0.01) which was again protective against suicide completion (P = 0.006). Single marker analysis showed the same protective effect of the rs891512 A-allele (P = 0.009) again especially against suicide completion (P = 0.007). Additionally, a second haplotype (T-T-G) was associated with increased aggression (P = 0.0002; sliding haplotype T-G, P = 0.002). In conclusion, our study suggests a possible involvement of NOS-I and NOS-III gene variants in suicidal behavior and related intermediate phenotypes. (C) 2007 Wiley-Liss, Inc.