An inducible nitric oxide synthase polymorphism is associated with the risk of recurrent depressive disorder

Evidence indicates that depressive disorder is a heterogenic disease, and oxidative stress, inflammation and impairment of neurogenesis play a role in its aetiology. Moreover, there are data suggesting that genetic factors affect the development of depression. Nitric oxide (NO) is a biological molecule with both a beneficial and a detrimental role in brain. One of the three enzymes generating NO is inducible nitric oxide synthase (iNOS). Recent studies have shown that depressed patients are characterised by excessive NO production. In addition, iNOS inhibitors are effective in depression treatment. This study investigated the importance of a functional single nucleotide polymorphism (SNP), -1026C/A, located in the promoter region of the human NOS2A gene, for the risk of recurrent depressive disorder (RDD) vulnerability. The study was carried out in a group of 181 patients with RDD and 149 ethnically matched controls. Genotyping was performed by direct sequencing of the polymerase chain reaction (PCR) products. The genotype distribution of the -1026C/A polymorphism between depressed patients and healthy controls was significantly different. Individuals who were homozygous for the CC genotype exhibited an increased risk of developing RDD. In conclusion we cautiously conclude that polymorphism in the NOS2A gene promoter may play a role in the background of RDD.