Further Evidence For Role Of Promoter Polymorphisms In Tnf Gene In Alzheimer'S Disease

Tumor necrosis factor (TNF) expression level is associated with regulating effects on Alzheimer's disease (AD) development. And several TNF SNPs have been reported to associate with AD, however, it is unclear whether TNF SNPs could affect TNF signaling. In this study, the effects of AD related TNF promoter SNPs (rs361525, rs1800629, rs1799724, rs1800630 and rs1799964) on the gene expression were explored by multiple large-scale expression quantitative trait loci (eQTL) datasets. We found that the five SNPs with minor allele could significantly regulate reduced TNF expression on different brain regions or whole blood sample in European population. Consistent with the result of eQTL analysis, we found rs1800630 A allele and rs1799964 C allele were significantly associated with increasing the volumes of brain amygdala based on the Enhancing Neuroimaging Genetics through Meta-Analysis database. These findings suggest that the promoter SNPs in TNF may play protective roles on AD risk. In addition, there was an interesting discovery that rs4248161 C allele significantly reduced the volumes of five brain regions, suggesting its potential risk for AD or other neuropathogenic diseases. Our studies could advance the understanding of the impact of TNF promoter SNPs in AD.