A common polymorphism in the 3'-UTR of the NOS1 gene was associated with completed suicides in Japanese male population.
BACKGROUND
Suicidal behavior has been widely accepted as familial. Its transmission cannot be explained by the transmission of psychiatric disorder alone and seems to be partly explained by the transmission of impulsive-aggressive behavior. Studies in laboratory animal have shown that mice lacking NOS1 manifest significant aggressive behavior. Further, several polymorphisms of neuronal nitric oxide synthase (NOS1) gene have been reported to be associated with impulsivity, aggression and suicide attempts. To further clarify the possible involvement of NOS1 with suicide, we carried out an association study of NOS1 gene polymorphisms with completed suicide.


METHODS
We examined 7 single nucleotide polymorphisms (SNPs) of the NOS1 gene which were previously studied in several neuropsychiatric disorders (rs2682826, rs6490121, rs3782206, rs561712, rs3782219, rs3782221, and rs41279104), in age and gender matched 287 healthy control subjects and 284 completed suicides using the TaqMan probe assays.


RESULTS
We found that both the genotypic distribution and the allelic frequencies of rs2682826 SNP were significantly different between the completed suicide and control groups (P=0.0007 and 0.0005, respectively). The odd ratio for the minor allele of the SNP was 0.653 (95% CI 0.513-0.832). The significance was remained even after correction for multiple testing. Gender-based analysis showed that the significances were appeared in males only.


CONCLUSIONS
Our study raises a possibility that a genetic variation of NOS1 may be implicated in the pathophysiology of suicide in Japanese population, especially in males. Further studies on more NOS1 genetic variants are needed to confirm our observations.
Cui
Huxing
H
Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Supriyanto
Irwan
I
Asano
Migiwa
M
Ueno
Yasuhiro
Y
Nagasaki
Yasushi
Y
Nishiguchi
Naoki
N
Shirakawa
Osamu
O
Hishimoto
Akitoyo
A
D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics; D008297:Male; D008875:Middle Aged; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013405:Suicide
D020413:3' Untranslated Regions; D052248:Nitric Oxide Synthase Type I