Elevated Global DNA Methylation Is Not Exclusive to Amyotrophic Lateral Sclerosis and Is Also Observed in Spinocerebellar Ataxia Types 1 and 2

Hamid Hamzeiy, Doruk Savaş, Ceren Tunca, Nesli Ece Şen, Asll Gündoǧdu Eken, Irmak Şahbaz, Daniela Calini, Cinzia Tiloca, Nicola Ticozzi, Antonia Ratti, Vincenzo Silani, A. Nazll Başak

Research output: Contribution to journalArticle


Adult-onset neurological disorders are caused and influenced by a multitude of different factors, including epigenetic modifications. Here, using an ELISA kit selected upon careful testing, we investigated global 5-methylcytosine (5-mC) levels in sporadic and familial amyotrophic lateral sclerosis (sALS and fALS), spinocerebellar ataxia types 1 and 2 (SCA1 and SCA2), Huntington's disease, Friedreich's ataxia, and myotonic dystrophy type 1. We report a significant elevation in global 5-mC levels of about 2-7% on average for sALS (p < 0.01 [F(1, 243) = 9.159, p = 0.0027]) and various forms of fALS along with SCA1 (p < 0.01 [F(1, 83) = 11.285], p = 0.0012) and SCA2 (p < 0.001 [F(1, 122) = 29.996, p = 0.0001]) when compared to age- and sex-matched healthy controls. C9orf72 expansion carrier ALS patients exhibit the highest global 5-mC levels along with C9orf72 promoter hypermethylation. We failed to measure global 5-hydroxymethylcytosine (5-hmC) levels in blood, probably due to the very low levels of 5-hmC and the limitations of the commercially available ELISA kits. Our results point towards a role for epigenetics modification in ALS, SCA1, and SCA2, and help conclude a dispute on the global 5-mC levels in sALS blood.

Original languageEnglish
Pages (from-to)38-48
Number of pages11
JournalNeurodegenerative Diseases
Issue number1
Publication statusPublished - Mar 1 2018



  • 5-Methylcytosine
  • Amyotrophic lateral sclerosis
  • Global DNA methylation
  • Spinocerebellar ataxia
  • Trinucleotide repeat disorder

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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