DNA methylation in the TNF-alpha gene decreases along with aging among delirium inpatients

Yamanashi, Takehiko; Saito, Taku; Yu, Tong; Alario, Alexandra; Crutchley, Kaitlyn J.; Sullivan, Eleanor J.; Anderson, Zoe-Ella M.; Marra, Pedro S.; Chang, Gloria; Wahba, Nadia E.; Jellison, Sydney S.; Meyer, Alissa A.; Mathur, Srishti; Pandharipande, Pratik; Yoshino, Aihide; Kaneko, Koichi; S, Lee; Toda, Hiroyuki; Iwata, Masaaki; Shinozaki, Gen

doi:10.1016/j.neurobiolaging.2021.05.005

Cited by 13 publications

(24 citation statements)

References 40 publications

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“…As previously described [ 14 – 16 , 18 ], DNA was isolated from blood with the MasterPureTM DNA extraction kit (Epicenter, MCD85201) following the respective protocols. DNA quality was assessed with NanoDrop spectrometry and quantity was assessed with the Qubit™ dsDNA Broad Range Assay Kit (ThermoFisher Scientific, Q32850).…”

Section: Methodsmentioning

confidence: 99%

“…DNAm of bisulfite-converted blood DNA samples were analyzed with the Infinium HumanMethylationEPIC BeadChip™ Kit (WG-317-1002, Illumina) as previously described [ 14 – 16 , 18 ]. The samples were placed on EPIC array chips randomly to avoid potential confounding batch effects.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Thirty-two CpG sites in the TNF gene were targeted in our pyrosequencing analyses as previously described [ 16 ]. Nested PCRs were conducted using bisulfite-converted DNA samples as previously described [ 16 ]. After nested PCRs, pyrosequencing was performed using PyroMark Q96 (Qiagen, #972804) and PyroMark Q24 Pyrosequencer (Qiagen, #9001514) to detect levels of DNA methylation.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously reported several epigenetic studies that investigated DNA methylation (DNAm) levels of delirium subjects [ 13 – 16 ]. For example, it was shown that DNAm levels in several CpG sites on the TNF gene were negatively correlated with age only in delirium subjects [ 16 ]. We also identified a genome-wide significant CpG at the LDLRAD4 gene [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation in the inflammatory genes after neurosurgery and diagnostic ability of post-operative delirium

et al. 2021

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The pathophysiological mechanisms of postoperative delirium (POD) are still not clear, and no reliable biomarker is available to differentiate those with and without POD. Pre- and post-surgery blood from epilepsy subjects undergoing neurosurgery were collected. DNA methylation (DNAm) levels of the TNF gene, IL1B gene, and IL6 gene by the Illumina EPIC array method, and DNAm levels of the TNF gene by pyrosequencing, were analyzed. Blood from 37 subjects were analyzed by the EPIC array method, and blood from 27 subjects were analyzed by pyrosequencing. Several CpGs in the TNF gene in preoperative blood showed a negative correlation between their DNAm and age both in the POD group and in the non-POD group. However, these negative correlations were observed only in the POD group after neurosurgery. Neurosurgery significantly altered DNAm levels at 17 out of 24 CpG sites on the TNF gene, 8 out of 14 CpG sites on the IL1B gene, and 4 out of 14 CpG sites on the IL6 gene. Furthermore, it was found that the Inflammatory Methylation Index (IMI), which was based on the post-surgery DNAm levels at the selected five CpG sites, can be a potential detection tool for delirium with moderate accuracy; area under the curve (AUC) value was 0.84. The moderate accuracy of this IMI was replicated using another cohort from our previous study, in which the AUC was 0.79. Our findings provide further evidence of the potential role of epigenetics and inflammation in the pathophysiology of delirium.

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Section: Methodsmentioning

confidence: 99%