TY - JOUR
T1 - Whole-blood global DNA methylation is increased in amyotrophic lateral sclerosis independently of age of onset
AU - Tremolizzo, Lucio
AU - Messina, Paolo
AU - Conti, Elisa
AU - Sala, Gessica
AU - Cecchi, Matteo
AU - Airoldi, Luisa
AU - Pastorelli, Roberta
AU - Pupillo, Elisabetta
AU - Bandettini Di Poggio, Monica
AU - Filosto, Massimiliano
AU - Lunetta, Christian
AU - Agliardi, Cristina
AU - Guerini, Franca
AU - Mandrioli, Jessica
AU - Calvo, Andrea
AU - Beghi, Ettore
AU - Ferrarese, Carlo
AU - Consortium, Eurals
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Age of onset
KW - Amyotrophic lateral sclerosis
KW - Blood
KW - DNA methylation
KW - Epigenetics
KW - Homocysteine
KW - Methionine
KW - Peripheral marker
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U2 - 10.3109/21678421.2013.851247
DO - 10.3109/21678421.2013.851247
M3 - Article
C2 - 24224837
AN - SCOPUS:84895524855
VL - 15
SP - 98
EP - 105
JO - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
JF - Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
SN - 2167-8421
IS - 1-2
ER -