The -308 (G/A) single nucleotide polymorphism in the TNF-alpha gene and the risk of major depression in the elderly

Abstract

Objective: The immune system (IS) plays a key role in the mechanisms underlying major depression (MD) and pro-inflammatory cytokines seem to be particularly involved in the pathogenesis of the disease. There is growing evidence of a relationship between commonly studied single nucleotide polymorphisms (SNPs) in cytokine genes and an increased risk of MD.The aim of our study was to investigate the association between the -308(G/A) SNP in the tumour necrosis factor-alpha (TNF-alpha) gene and late-life MD in elderly people without dementia.

Methods: Blood samples were obtained from 50 subjects enrolled at the Geriatric Department of the San Gerardo Hospital in Monza, Italy, after screening with the geriatric depression scale (GDS > or = 15) and mini-mental state evaluation (MMSE > or = 24). The -308 (G/A) SNP was genotyped by SSP-PCR amplification. Two hundred and forty age-matched healthy volunteers were taken as the control group.

Results: Genotype and allele distributions in patients with MD were significantly different from those of the controls. In subjects affected by MD we found a higher percentage of the GG genotype (84 vs. 68,3%; p = 0.007) and thus of the G allele (92 vs. 81,9%; p = 0.05).The GG genotype was associated with a greater risk of developing the disease (OR 2.433, CI 1.09-5.43).

Conclusions: Our study suggests that the -308 (G/A) polymorphism in the TNF-alpha gene could play a role in determining susceptibility to MD. An activation of the TNF-alpha system could contribute to the development of MD in the elderly.