Whole-blood global DNA methylation is increased in amyotrophic lateral sclerosis independently of age of onset.
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 [(3)H]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.
Department of Neurology, 'San Gerardo' Hospital and University of Milano-Bicocca , Monza.
Lucio
L
Tremolizzo
Paolo
P
Messina
Elisa
E
Conti
Gessica
G
Sala
Matteo
M
Cecchi
Luisa
L
Airoldi
Roberta
R
Pastorelli
Elisabetta
E
Pupillo
Monica
M
Bandettini Di Poggio
Massimiliano
M
Filosto
Christian
C
Lunetta
Cristina
C
Agliardi
Franca
F
Guerini
Jessica
J
Mandrioli
Andrea
A
Calvo
Ettore
E
Beghi
Carlo
C
Ferrarese
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000235:genetics*; D000704:Analysis of Variance; D002853:Chromatography, Liquid; D019175:DNA Methylation / Q000235:genetics*; D003845:Deoxycytosine Nucleotides; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008715:Methionine / Q000097:blood; D008875:Middle Aged; D012372:ROC Curve; D014316:Tritium
D003845:Deoxycytosine Nucleotides; D006710:Homocysteine; D014316:Tritium; C024107:2'-deoxycytidine 5'-triphosphate; D008715:Methionine