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

• Published in: Amyotrophic lateral sclerosis and frontotemporal degeneration Vol. 15; no. 1-2; pp. 98 - 105
• Main Authors: Tremolizzo, Lucio, Messina, Paolo, Conti, Elisa, Sala, Gessica, Cecchi, Matteo, Airoldi, Luisa, Pastorelli, Roberta, Pupillo, Elisabetta, Bandettini Di Poggio, Monica, Filosto, Massimiliano, Lunetta, Christian, Agliardi, Cristina, Guerini, Franca, Mandrioli, Jessica, Calvo, Andrea, Beghi, Ettore, Ferrarese, Carlo
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.03.2014; Taylor & Francis
• Subjects: Adult; Age of Onset; Aged; Aged, 80 and over; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - blood; Amyotrophic Lateral Sclerosis - genetics; Analysis of Variance; blood; Chromatography, Liquid; Deoxycytosine Nucleotides; DNA methylation; DNA Methylation - genetics; epigenetics; Female; homocysteine; Homocysteine - blood; Humans; Male; methionine; Methionine - blood; Middle Aged; peripheral marker; ROC Curve; Tritium
• ISSN: 2167-8421; 2167-9223
• DOI: 10.3109/21678421.2013.851247

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.