AUTHOR=Juárez-Cedillo Teresa , Martínez-Rodríguez Nancy , Vargas-Alarcon Gilberto , Juárez-Cedillo Enrique , Valle-Medina Antonio , Garrido-Acosta Osvaldo , Ramirez Alfredo 

TITLE=Synergistic influence of cytokine gene polymorphisms over the risk of dementia: A multifactor dimensionality reduction analysis

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.952173

DOI=10.3389/fnagi.2022.952173

ISSN=1663-4365

ABSTRACT=<sec><title>Objective</title><p>Evidence supports the important role of neuroinflammation in some types of dementia. This study aimed to evaluate the effect of epistasis of gene cytokines such as interleukin (IL)-α, IL-6, tumor necrosis factor (TNFα), and interferon-gamma (IFN-γ) on the susceptibility to the development of dementia.</p></sec><sec><title>Materials and methods</title><p>In the study, 221 patients diagnosed with dementia and 710 controls were included. The multifactor-dimensionality reduction (MDR) analysis was performed to identify the epistasis between SNP located in genes of IL-α (rs1800587), IL-6 (rs1800796), TNFα (rs361525 and rs1800629), and IFNγ (rs2069705). The best risk prediction model was identified based on precision and cross-validation consistency.</p></sec><sec><title>Results</title><p>Multifactor-dimensionality reduction analysis detected a significant model with the genes TNFα, IFNγ, IL1α, and IL6 (prediction success: 72%, <italic>p</italic> &lt; 0.0001). When risk factors were analyzed with these polymorphisms, the model achieved a similar prediction for dementia as the genes-only model.</p></sec><sec><title>Conclusion</title><p>These data indicate that gene–gene interactions form significant models to identify populations susceptible to dementia.</p></sec>