DNA methylation in ELOVL2 and C1orf132 correctly predicted chronological age of individuals from three disease groups

Abstract

Improving accuracy of the available predictive DNA methods is important for their wider use in routine forensic work. Information on age in the process of identification of an unknown individual may provide important hints that can speed up the process of investigation. DNA methylation markers have been demonstrated to provide accurate age estimation in forensics, but there is growing evidence that DNA methylation can be modified by various factors including diseases. We analyzed DNA methylation profile in five markers from five different genes (ELOVL2, C1orf132, KLF14, FHL2, and TRIM59) used for forensic age prediction in three groups of individuals with diagnosed medical conditions. The obtained results showed that the selected age-related CpG sites have unchanged age prediction capacity in the group of late onset Alzheimer’s disease patients. Aberrant hypermethylation and decreased prediction accuracy were found for TRIM59 and KLF14 markers in the group of early onset Alzheimer’s disease suggesting accelerated aging of patients. In the Graves’ disease patients, altered DNA methylation profile and modified age prediction accuracy were noted for TRIM59 and FHL2 with aberrant hypermethylation observed for the former and aberrant hypomethylation for the latter. Our work emphasizes high utility of the ELOVL2 and C1orf132 markers for prediction of chronological age in forensics by showing unchanged prediction accuracy in individuals affected by three diseases. The study also demonstrates that artificial neural networks could be a convenient alternative for the forensic predictive DNA analyses.

A longitudinal, epigenome-wide study of DNA methylation in anorexia nervosa: results in actively ill, partially weight-restored, long-term remitted and non-eating-disordered women

“…26 Among the probes most strongly associated with illness duration, we found ELOVL2 and FHL2, both of which have been associated with epigenetic age and agerelated condi tions. 39,40,45,46 It is an intuitive point that the length of a per son's exposure to anorexia nervosa is likely to be detrimental to their health prospects, and our findings suggest that sev eral adverse effects of this type may be epigenetically regu lated. Consistent with possible effects of the underconsump tion of nutrients implicated in DNA methylation, illness chronicity was inversely correlated with methylation levels at most of the implicated probes: greater duration of illness was associated with lower methylation.…”

“…Finally, the analysis isolated probes related to wound healing (TNXB), taste (TAS1R3), insulin metabolism (IRS2, RPTOR), skeletal homeostasis (LRP5) and agerelated conditions (e.g., ELOVL2, FHL2). 39,40 The direction of differ ences (on 39 of 64 [60.9%] differentially methylated probes) suggested a trend toward lower methylation in people with more chronic anorexia nervosa. Among identified genes, PRRT1, ZNRF2, RPTOR, NRXN2, SPTA1 and LRP5 were also isolated in the active versus remitted versus NED compari son described earlier.…”

Age Estimation Based on DNA Methylation Using Blood Samples From Deceased Individuals

“…The ELOVL2 marker correlated highly with age and showed only slight differences between CpG sites, in a similar way to the previous studies with whole blood using other methodologies. The obtained differences in DNA methylation accuracy of age markers, with ELOVL2 as exception, could be explained by modifications on the methylation status of the studied genes by various factors including diseases . The possibility that postmortem changes can alter the methylation status among specific loci should also be hypothesized, although this issue has not yet been clarified until now .…”

The role of KLF14 in multiple disease processes

“…In this study, it is found that KLF14 induced the epigenetic regulation of the chromatin organization and mRNA processing together with the TRIM59 during the G2/M phase of the cell cycle phase, and BRCA1 protein during DNA repair process, and in turn contributed to pro‐apoptotic signaling in AD. In another study, degree of KLF14 methylation was compared in three groups of recruited patients (Patients with fEOAD, late‐onset AD, as well as normal control) to evaluate if it could provide information about age of disease onset. Interestingly, the obtained results showed no difference of the methylation level among the group of late‐onset Alzheimer's disease patients while the methylation level of fEOAD patients were abnormally elevated.…”