Whole-blood global DNA methylation is increased in amyotrophic lateral sclerosis independently of age of onset

Lucio Tremolizzo, Paolo Messina, Elisa Conti, Gessica Sala, Matteo Cecchi, Luisa Airoldi, Roberta Pastorelli, Elisabetta Pupillo, Monica Bandettini Di Poggio, Massimiliano Filosto, Christian Lunetta, Cristina Agliardi, Franca Guerini, Jessica Mandrioli, Andrea Calvo, Ettore Beghi, Carlo Ferrarese, Eurals Consortium

Research output: Contribution to journalArticle

Abstract

ALS is a heterogeneous disease that is not well understood. Epigenetic rearrangements are important in complex disorders including motor neuron diseases. The aim of this study was to determine whether whole-blood DNA methylation (DNA MET %) is a potential modifier of age at onset in ALS. DNA MET % was measured as incorporation of [3H]dCTP following HpaII cut in 96 ALS patients and 87 controls, comprising: early-onset (<55 years of age) and late-onset (> 74 years of age). Methionine (Met) and homocysteine (Hcy) plasma levels were assessed by liquid chromatography selected reaction monitoring coupled with isotope-dilution mass spectrometry. Results showed that DNA MET % was increased in ALS patients independently of age of onset. Compared to the other three groups, Hcy plasma levels were reduced in early-onset ALS patients but Met levels were similar. ROC analysis reported Met levels and DNA MET %, respectively, with a slight and moderate discriminative power. In conclusion, increased DNA MET % is a possible marker of epigenetic dysfunction in ALS independently of age of onset. Further studies dissecting biological determinants of phenotypic complexity in ALS may help in developing successful therapeutic strategies.

Original languageEnglish
Pages (from-to)98-105
Number of pages8
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Volume15
Issue number1-2
DOIs
Publication statusPublished - 2014

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Keywords

  • Age of onset
  • Amyotrophic lateral sclerosis
  • Blood
  • DNA methylation
  • Epigenetics
  • Homocysteine
  • Methionine
  • Peripheral marker

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Tremolizzo, L., Messina, P., Conti, E., Sala, G., Cecchi, M., Airoldi, L., Pastorelli, R., Pupillo, E., Bandettini Di Poggio, M., Filosto, M., Lunetta, C., Agliardi, C., Guerini, F., Mandrioli, J., Calvo, A., Beghi, E., Ferrarese, C., & Consortium, E. (2014). Whole-blood global DNA methylation is increased in amyotrophic lateral sclerosis independently of age of onset. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 15(1-2), 98-105. https://doi.org/10.3109/21678421.2013.851247