Evidence for Type-Specific DNA Methylation Patterns in Epilepsy: A Discordant Monozygotic Twin Approach

Mohandas, Namitha; Loke, Yuk Jing; Hopkins, Stephanie; Mackenzie, Lisa; Bennett, Carmen; Berkovic, Samuel F.; Vadlamudi, Lata; Craig, Jeffrey M.

doi:10.2217/epi-2018-0136

Cited by 20 publications

(11 citation statements)

References 73 publications

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“…Finally, it is important to highlight the role of PM20D1 in neurological disorders. In addition to its involvement in AD and PD (as detailed in previous sections), hypermethylation of CpG sites in PM20D1 (and presumably reduced expression) has been associated with an increased risk of suffering chronic postsurgical pain [102] . Additionally, it has been reported that PM20D1 is differentially methylated between different types of epilepsy (focal vs. generalized epilepsy) [103] .…”

Section: Other Phenotypesmentioning

confidence: 90%

The many roles of the Alzheimer-associated gene PM20D1

Garro-Núñez¹,

Mora-Cubillo²,

Fonseca-Bone³

et al. 2022

J Transl Genet Genom

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PM20D1 is a little studied enzyme until recently, belonging to the mammalian M20 peptidase family, which catalyzes both the synthesis and hydrolysis of N-acyl amino acids (NAAs). NAAs are bioactive lipids biosynthesized from free fatty acids and free amino acids. These molecules have been associated with many biological functions; however, most of the biochemical mechanisms have not yet been described. The best-known biochemical mechanism is the one involved in thermogenesis, which also has implications for reactive oxygen species levels and cell preservation. In the last few years, genetic variation in PM20D1, as well as changes in its methylation and expression levels, have been reported to be associated with several disease phenotypes, including Alzheimer’s disease. In this review, we explore the current knowledge regarding the PM20D1 gene, including aspects such as its biology, potential functions, regulation of its expression, and role in different phenotypes such as Alzheimer’s disease, obesity, Parkinson’s disease, and several other disorders.

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Section: Other Phenotypesmentioning

confidence: 90%

The many roles of the Alzheimer-associated gene PM20D1

Garro-Núñez¹,

Mora-Cubillo²,

Fonseca-Bone³

et al. 2022

J Transl Genet Genom

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“…The proportion of epithelial cells in oral samples estimated from cytology and DNA methylation was tested using Pearson correlation coefficient. To investigate the age effect on epithelial cell content estimated using DNA methylation, the buccal and saliva sample data from this study was analysed along with seven of our other studies, three published (3,10,11) and four unpublished. These cohorts' details included to investigate the age effect on epithelial cell content was described in supplementary method.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous paper, we observed that epithelial cell content of buccal swabs and saliva was lower in adults compared to children (3). To investigate a possible age effect using epithelial cell content estimated using DNA methylation, we combined buccal swab and saliva data from this study with seven of our other Infinium array studies, including three published (3,10,11) and four unpublished (Figure 5, Supplementary Table 2). We found a moderate negative correlation between age and epithelial cell content estimated by DNA methylation (R = -0.72, p <0.0001, 0.59% of epithelial cell content estimated from DNA methylation), with age accounting for 14% of the variation in epithelial cell content.…”

Section: An Age Effect On Epithelial Cell Content In Salivamentioning

confidence: 99%

“…As stated in the method, to investigate the age effect on epithelial cell content estimated using DNA methylation, the buccal and saliva sample data from this study was analysed along with three published (3,10,11) and four unpublished of our other studies. First, the child participants are recruited from part of the Peri/postnatal Epigenetic Twins Study (PETS) cohort, an Australian twin birth research study based in Melbourne.…”

Section: Disclosure Of Interestmentioning

confidence: 99%

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A comparison of epithelial cell content of oral samples estimated using cytology and DNA methylation

Wong

Tayeb²,

Stone³

et al. 2021

Epigenetics

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Saliva and buccal samples are popular for epigenome wide association studies (EWAS) due to their ease of collection compared and their ability to sample a different cell lineage compared to blood. As these samples contain a mix of white blood cells and buccal epithelial cells that can vary within a population, this cellular heterogeneity may confound EWAS. This has been addressed by including cellular heterogeneity obtained through cytology at the time of collection or by using cellular deconvolution algorithms built on epigenetic data from specific cell types. However, to our knowledge, the two methods have not yet been compared. Here we show that the two methods are highly correlated in saliva and buccal samples (R = 0.84, P <0.0001) by comparing data generated from cytological staining and Infinium MethylationEPIC arrays and the EpiDISH deconvolution algorithm from buccal and saliva samples collected from twenty adults. In addition, by using an expanded dataset from both sample types, we confirmed our previous finding that age has a significant negative correlation with epithelial cell proportion in both sample types. However, children and adults showed a large within-population variation in cellular heterogeneity. Our results validate the use of the EpiDISH algorithm in estimating the effect of cellular heterogeneity in EWAS and showed DNA methylation generally underestimates the epithelial cell content obtained from cytology.

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“…Another important issue worth mentioning is the role of DNAm for diagnostic and prognostic approaches in epilepsy. As an example, the blood of patients with mTLE-HS has shown specific DNAm patterns (Long et al, 2017) and a concordant-twin study detected patterns that enabled distinction between focal and generalized epilepsy (Mohandas et al, 2019). These results suggest that blood-based DNAm could be a potential biomarker for epilepsy and epileptogenesis, paving the way to a more personalized management of people with epilepsy (PWE).…”

Section: Potential Strategies and Challenges Of Anti-epileptogenic In...mentioning

confidence: 92%

The potential role of DNA methylation as preventive treatment target of epileptogenesis

Berger

Taubøll

2022

Front. Cell. Neurosci.

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Pharmacological therapy of epilepsy has so far been limited to symptomatic treatment aimed at neuronal targets, with the result of an unchanged high proportion of patients lacking seizure control. The dissection of the intricate pathological mechanisms that transform normal brain matter to a focus for epileptic seizures—the process of epileptogenesis—could yield targets for novel treatment strategies preventing the development or progression of epilepsy. While many pathological features of epileptogenesis have been identified, obvious shortcomings in drug development are now believed to be based on the lack of knowledge of molecular upstream mechanisms, such as DNA methylation (DNAm), and as well as a failure to recognize glial cell involvement in epileptogenesis. This article highlights the potential role of DNAm and related gene expression (GE) as a treatment target in epileptogenesis.

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Evidence for Type-Specific DNA Methylation Patterns in Epilepsy: A Discordant Monozygotic Twin Approach

Cited by 20 publications

References 73 publications

The many roles of the Alzheimer-associated gene PM20D1

The many roles of the Alzheimer-associated gene PM20D1

A comparison of epithelial cell content of oral samples estimated using cytology and DNA methylation

The potential role of DNA methylation as preventive treatment target of epileptogenesis

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