-308(G/A) TNF-alpha gene polymorphism and risk of depression late in the life

Abstract

The relationship between major depression (MD) and dementia in the elderly is still not clear, but it is certain that the immune system and in particular, pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, play a key role in the mechanisms underlying the two neuro-psychiatric disorders. In our experience, the -308(G/A) single nucleotide polymorphism (SNP) in the TNF-alpha gene is associated with earlier age at onset in patients affected by Alzheimer's disease (AD). The aim of this study was to investigate the association between the -308(G/A) SNP and late-life MD in elderly people without dementia. Blood samples were obtained from 50 subjects, after screening with the geriatric depression scale (GDS>or=15) and mini-mental state examination (MMSE>or=24). The -308 (G/A) SNP was genotyped by SSP-PCR amplification. Two-hundred-fourty age-matched healthy volunteers were taken as the control group. We identified different genotype and allele distributions of the SNP in old depressed patients and healthy controls (HC). Our results evidenced a significantly higher percentage of the GG genotype in depressed subjects (84.0% vs. 68.3%; p=0.007) and consequently of the G allele (92.0% vs. 81.9%; p=0.05). The presence of the GG genotype raised the risk of developing MD (odds ratio=OR=2.433, confidence interval=Cl=1.09-5.43). Our findings suggested that the investigated TNF-alpha SNP may: (1) affect MD susceptibility; (2) be involved both in AD and MD development, but probably with a distinct role in the two pathologies.