Elsevier

Neuroscience Letters

Volume 486, Issue 3, 17 December 2010, Pages 184-187
Neuroscience Letters

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

https://doi.org/10.1016/j.neulet.2010.09.048Get rights and content

Abstract

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.

Research highlights

NOS2A gene is related to depression. ▶ Functional polymorphism −1026C/A of the NOS2A affects depression. ▶ The C allele and CC homozygote in −1026C/A are positive risk factors for depression.

References (49)

  • C.V. Suschek et al.

    Nitric oxide fully protects against UVA-induced apoptosis in tight correlation with Bcl-2 up-regulation

    J. Biol. Chem.

    (1999)
  • E. Suzuki et al.

    Elevated plasma nitrate levels in depressive states

    J. Affect. Disord.

    (2001)
  • M. Valko et al.

    Free radicals and antioxidants in normal physiological functions and human disease

    Int. J. Biochem. Cell. Biol.

    (2007)
  • D. Wang et al.

    Prevention of chronic stress-induced depression-like behavior by inducible nitric oxide inhibitor

    Neurosci. Lett.

    (2008)
  • G. Wegener et al.

    Local, but not systemic, administration of serotonergic antidepressants decreases hippocampal nitric oxide synthase activity

    Brain Res.

    (2003)
  • J.S. Beckamnn

    Peroxynitrite versus hydroxyl radical: the role of nitric oxide in superoxide dependent cerebral injury

    Ann. N. Y. Acad. Sci.

    (1994)
  • J.M. Bland et al.

    Statistics notes, the odds ratio

    BMJ

    (2000)
  • C. Bogdan

    Nitric oxide and the immune response

    Nat. Immunol.

    (2001)
  • S. Brahmachari et al.

    Sodium benzoate, a metabolite of cinnamon and a food additive, reduces microglial and astroglial inflammatory responses

    J. Immunol.

    (2009)
  • G.C. Brown

    Mechanisms of inflammatory neurodegeneration: iNOS and NADPH oxidase

    Biochem. Soc. Trans.

    (2007)
  • A. Cárdenas et al.

    Implication of glutamate in the expression of inducible nitric oxide synthase after oxygen and glucose deprivation in rat forebrain slices

    J. Neurochem.

    (2000)
  • P. Chomczyński

    A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples

    Biotechniques

    (1993)
  • K.C. Chung et al.

    Tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate differentially modulate cytotoxic effect of nitric oxide generated by serum deprivation in neuronal PC12 cells

    J. Neurochem.

    (1999)
  • F. Crespi

    The selective serotonin reuptake inhibitor fluoxetine reduces striatal in vivo levels of voltammetric nitric oxide (NO): a feature of its antidepressant activity?

    Neurosci. Lett.

    (2009)
  • Cited by (0)

    View full text