Aims: 

Both the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) and the vascular endothelial growth factor (VEGF), a neurotropic protein, have been implicated in the pathophysiology of certain disorders of the central nervous system including depression and dementia. Here, we present an association study between major depressive disorder (MDD) and several single nucleotide polymorphisms (SNP) located either in the 5' regulatory or in the coding regions of these genes and known to influence either the expression level or the activity of these proteins.

Methods: 

250 in-patients suffering from MDD and 428 healthy volunteers were enrolled in the study. MDD was diagnosed according to DSM-IV criteria and evaluated with the Montgomery-Asberg Depression Scale (MADRS). DNA was isolated from buccal cells and five functional SNPs (rs1800629, rs 1800630 and rs361525 in the TNF-a gene; rs699947 and rs2010963 in the VEGF gene) were analyzed in quantitative PCR-based genotyping assays using allele-specific TaqMan probes. Statistical evaluation was performed by the SPSS 17.0 software.

Results: 

A significant difference was identified in the genotype distribution of the TNF-a +308 A/G (rs1800629) SNP between the patient and the control groups. The frequency of the homozygous AA genotype was 2.45 fold higher among healthy individuals than in the population of MDD patients (4.9% versus 2.0%, respectively; LRT=4.197, p=0.040), while the A allele frequency was markedly higher in the control group (16.7% vs. 15.6%).

Conclusion: 

Our data suggest that the A variant of the TNF-a +308 A/G SNP, that has been previously associated with increased cytokine expression and plasma levels, might play a protective role against the development of major depressive disorder.

Support: 

OTKA CK 80289 national grant