Association between inducible and neuronal nitric oxide synthase polymorphisms and recurrent depressive disorder.
BACKGROUND
Major depression is characterised by increased nitric oxide (NO) levels. Inhibition of the NO synthesizing enzymes, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS), results in antidepressant-like effects, whereas the expression of iNOS and nNOS is increased in depression. Recent studies have indicated that NOS participates in the mechanisms of antidepressants. The aim of this study was to examine whether a single nucleotide polymorphism (SNP) present in the genes encoding iNOS and nNOS can contribute to the risk of developing recurrent depressive disorder (rDD).


METHODS
The study was carried out in a group of 181 depressive patients and 149 control subjects of Polish origin. SNPs were assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses.


RESULTS
The genotype distributions of the polymorphisms in exon 22 of the NOS2A gene and in exon 29 of the nNOS gene were significantly different between rDD patients and controls. The results showed that the G/A SNP of the gene encoding iNOS was associated with an increased susceptibility to rDD, whereas A/A homozygous carriers had a decreased risk of developing rDD. There was also a significant association between the C/T SNP of the gene encoding nNOS; the presence of the CC homozygous genotype decreased the risk of rDD, whereas the T allele and T/T homozygous genotype increased the vulnerability to rDD.


CONCLUSIONS
Our results suggest that polymorphisms in the iNOS and nNOS genes confer an increased susceptibility or resistance to rDD. Future research should examine genetic variants and their associations to the expression of NOSs and NO level in depressive patients.
Gałecki
Piotr
P
Department of Adult Psychiatry, Medical University of Łódź, Poland. piotr.galecki@umed.lodz.pl
Maes
Michael
M
Florkowski
Antoni
A
Lewiński
Andrzej
A
Gałecka
Elżbieta
E
Bieńkiewicz
Małgorzata
M
Szemraj
Janusz
J
D000328:Adult; D003866:Depressive Disorder / Q000201:enzymology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
C496320:NOS1 protein, human; C496319:NOS2 protein, human; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II