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.

Elevated global DNA methylation is not exclusive to amyotrophic lateral sclerosis and is also observed in spinocerebellar ataxia types 1 and 2 / H. Hamzeiy, D. Savaş, C. Tunca, N.E. Şen, A. Gündoğdu Eken, I. Şahbaz, D. Calini, C. Tiloca, N. Ticozzi, A. Ratti, V. Silani, A.N. Başak. - In: NEURODEGENERATIVE DISEASES. - ISSN 1660-2854. - 18:1(2018 Mar), pp. 38-48. [10.1159/000486201]

Elevated global DNA methylation is not exclusive to amyotrophic lateral sclerosis and is also observed in spinocerebellar ataxia types 1 and 2

C. Tiloca;N. Ticozzi;A. Ratti;V. Silani;
2018

Abstract

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.
5-Methylcytosine; amyotrophic lateral sclerosis; ELISA; global DNA methylation; spinocerebellar ataxia; trinucleotide repeat disorder
Settore MED/26 - Neurologia
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
mar-2018
9-feb-2018
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/549082
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