Methylation of IL-6 & TNF-α Associated Genes in Cognitive Impairment: A Texas Alzheimer's Research & Care Consortium (TARCC) Study




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Purpose: The Mexican American (MA) population poses one of the highest risk groups for the development of Alzheimer’s Disease (AD). Inflammatory biomarkers, such as IL-6 and TNF-a, have been associated with cognitive decline but most only in non-Hispanic Whites (NHWs). Epigenetic DNA methylation of CpG islands associated with inflammatory markers (IL-6 and TNF-a) have been studied and identified in other diseases but literature for its effects on cognitive impairment (CI), especially in MAs, is quite sparse. This study aims to determine if DNA methylation of CpG islands for IL-6 and TNF-a are associated with CI in a MA and NHW cohort. Methods: Utilizing the TARCC cohort (N = 551), participants within ethnic groups (N = 299 MAs, N = 252 NHWs) were stratified by cognitive status (normal cognition (NC) or CI). Methylation data at CpG sites were measured as beta values by array probes using the Illumina EPIC array. Linear regression analysis was performed in R comparing the beta value and cognitive diagnosis (NC or CI) for MA and NHW. Covariates include age, sex, education, CD8T cells, CD4T cells, B cells, monocytes, neutrophils, and the APOE gene. Result: The methylation sites cg04381957 and cg04583842 (both associated with IL-6) were significant within MAs. Those sites suggest hypomethylation and hypermethylation, respectively, in CI compared to the NC. Methylation site cg16411857 (associated with TNF-a) was not significant with CI in either MAs or NHWs. Conclusion: There was a stronger association with IL-6 related CpG sites and CI especially in MA at cg04381957 (p = 0.0035) within the RFTN1 gene. Future research plans to include inflammatory syndromes, such as diabetes, which could be a potential confounding variable affecting levels of IL-6 or TNF-a.