Abstract
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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Hardy, J., Selkoe, D.J.: The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580), 353–356 (2002)
Bertram, L., et al.: Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat. Genet. 39(1), 17–23 (2007)
Lambert, J.C., et al.: Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat. Genet. 41(10), 1088–1093 (2009)
Rezazadeh, M., et al.: Genetic factors affecting late-onset Alzheimer’s disease susceptibility. NeuroMol. Med. 18(1), 37–49 (2016)
Bagyinszky, E., et al.: Role of inflammatory molecules in the Alzheimer’s disease progression and diagnosis. J. Neurol. Sci. 376, 242–254 (2017)
Chang, R., Yee, K.L., Sumbria, R.K.: Tumor necrosis factor alpha inhibition for Alzheimer’s disease. J. Cent. Nerv. Syst. Dis. 9, 1–5 (2017)
Tarkowski, E., et al.: TNF gene polymorphism and its relation to intracerebral production of TNFalpha and TNFbeta in AD. Neurology 54(11), 2077–2081 (2000)
Tarkowski, E., et al.: Intrathecal inflammation precedes development of Alzheimer’s disease. J. Neurol Neurosur. Ps. 74(9), 1200–1205 (2003)
Ardebili, S.M., et al.: Genetic association of TNF-alpha-308 G/A and -863 C/A polymorphisms with late onset Alzheimer’s disease in Azeri Turk population of Iran. J. Res. Med. Sci. 16(8), 1006–1013 (2011)
Gnjec, A., et al.: Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer’s disease. J. Neuroinflamm. 5, 36 (2008)
Ma, S.L., et al.: Association between tumor necrosis factor-alpha promoter polymorphism and Alzheimer’s disease. Neurology 62(2), 307–309 (2004)
Kollias, G.: TNF pathophysiology in murine models of chronic inflammation and autoimmunity. Semin. Arthritis Rheum. 34(5 Suppl1), 3–6 (2005)
Ramasamy, A., et al.: Genetic variability in the regulation of gene expression in ten regions of the human brain. Nat. Neurosci. 17(10), 1418–1428 (2014)
Consortium, G.: The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348(6235), 648–660 (2015)
Westra, H.J., et al.: Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat. Genet. 45(10), 1238–1243 (2013)
Zou, F., et al.: Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants. PLoS Genet. 8(6), e1002707 (2012)
Shabalin, A.A.: Matrix eQTL: ultra fast eQTL analysis via large matrix operations. Bioinformatics 28(10), 1353–1358 (2012)
Murthy, M.N., et al.: Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson’s disease on chromosome 7p15.3. Neurogenetics 18(3), 121–133 (2017)
Thompson, P.M., et al.: ENIGMA and the individual: predicting factors that affect the brain in 35 countries worldwide. Neuroimage 145(Pt B), 389–408 (2017)
Adams, H.H.H., et al.: Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nat. Neurosci. 19(12), 1569–1582 (2016)
Culpan, D., et al.: Tumour necrosis factor-alpha gene polymorphisms and Alzheimer’s disease. Neurosci. Lett. 350(1), 61–65 (2003)
Flex, A., et al.: Effect of proinflammatory gene polymorphisms on the risk of Alzheimer’s disease. Neurodegener Dis. 13(4), 230–236 (2014)
Liu, G., et al.: Genetic variant rs763361 regulates multiple sclerosis CD226 gene expression. Proc. Natl. Acad. Sci. U.S.A. 114(6), E906–e907 (2017)
Wang, T.: TNF-alpha G308A polymorphism and the susceptibility to Alzheimer’s disease: an updated meta-analysis. Arch. Med. Res. 46(1), 24–30 (2015)
Bona, D.D., et al.: Systematic review by meta-analyses on the possible role of TNF-α polymorphisms in association with Alzheimer’s disease. Brain Res. Rev. 61(2), 60–68 (2009)
Qidwai, T., Jamal, F., Khan, M.Y.: DNA sequence variation and regulation of genes involved in pathogenesis of pulmonary tuberculosis. Scand. J. Immunol. 75(6), 568–587 (2012)
Jin, X., Zhou, B., Zhang, D.: Replication study confirms the association of the common rs1800629 variant of the TNF gene with postmenopausal osteoporosis susceptibility in the han chinese population. Genet. Test Mol. Biomark. 22(4), 246–251 (2018)
Acknowledgement
The authors thank the members of our laboratory for their valuable discussions. This work has been supported by the grants from the National Natural Science Foundation of China (61672037 and 21601001), the Initial Foundation of Doctoral Scientific Research in Anhui University (J01001319) and the Initial Foundation of Postdoctoral Scientific Research in Anhui University (J01002047).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this paper
Cite this paper
Bin, Y., Shu, L., Zhu, Q., Zhu, H., Xia, J. (2018). Further Evidence for Role of Promoter Polymorphisms in TNF Gene in Alzheimer’s Disease. In: Huang, DS., Jo, KH., Zhang, XL. (eds) Intelligent Computing Theories and Application. ICIC 2018. Lecture Notes in Computer Science(), vol 10955. Springer, Cham. https://doi.org/10.1007/978-3-319-95933-7_54
Download citation
DOI: https://doi.org/10.1007/978-3-319-95933-7_54
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-95932-0
Online ISBN: 978-3-319-95933-7
eBook Packages: Computer ScienceComputer Science (R0)