{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:19:28Z","timestamp":1778786368543,"version":"3.51.4"},"reference-count":88,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurodegener Dis"],"published-print":{"date-parts":[[2018]]},"abstract":"<jats:p>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\u2019s disease, Friedreich\u2019s ataxia, and myotonic dystrophy type 1. We report a significant elevation in global 5-mC levels of about 2\u20137% on average for sALS (&lt;i&gt;p&lt;\/i&gt; &amp;#x3c; 0.01 [F(1, 243) = 9.159, &lt;i&gt;p&lt;\/i&gt; = 0.0027]) and various forms of fALS along with SCA1 (&lt;i&gt;p&lt;\/i&gt; &amp;#x3c; 0.01 [F(1, 83) = 11.285], &lt;i&gt;p&lt;\/i&gt; = 0.0012) and SCA2 (&lt;i&gt;p&lt;\/i&gt; &amp;#x3c; 0.001 [F(1, 122) = 29.996, &lt;i&gt;p&lt;\/i&gt; = 0.0001]) when compared to age- and sex-matched healthy controls. &lt;i&gt;C9orf72&lt;\/i&gt; expansion carrier ALS patients exhibit the highest global 5-mC levels along with &lt;i&gt;C9orf72&lt;\/i&gt; 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.<\/jats:p>","DOI":"10.1159\/000486201","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T22:01:29Z","timestamp":1518213689000},"page":"38-48","source":"Crossref","is-referenced-by-count":29,"title":["Elevated Global DNA Methylation Is Not Exclusive to Amyotrophic Lateral Sclerosis and Is Also Observed in Spinocerebellar Ataxia Types 1 and 2"],"prefix":"10.1159","volume":"18","author":[{"given":"Hamid","family":"Hamzeiy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doruk","family":"Sava\u015f","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ceren","family":"Tunca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nesli\u00a0Ece","family":"\u015een","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asl\u0131","family":"G\u00fcndo\u011fdu\u00a0Eken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irmak","family":"\u015eahbaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Calini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Tiloca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Ticozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Ratti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Silani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.\u00a0Nazl\u0131","family":"Ba\u015fak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2018,2,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.59"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2341"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2014.08.015"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2015.06.052"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8935-6-10"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-120213-092518"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-014-0060-z"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3584"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2014.959024"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.2146\/news170039"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.011"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.09.010"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1177\/1073858414555404"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052672"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2013.851247"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-013-0205-6"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1639-11.2011"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1401-8"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.04.017"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.02.015"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1365-0"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.159"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu576"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2014.07.003"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812448534"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199902)45:2<200::AID-ANA10>3.0.CO;2-U"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/nature09320"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr227"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.04.016"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1038\/nature22038"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-1101-y"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2004.03.046"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-013-0206-5"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.10.060"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.3233\/JHD-159001"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22671"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.058594"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm346"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60382-2"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.10.1919"},{"key":"ref41","doi-asserted-by":"publisher","DOI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