Methylation levels of SLC23A2 and NCOR2 genes correlate with spinal muscular atrophy severity

PLoS One. 2015 Mar 30;10(3):e0121964. doi: 10.1371/journal.pone.0121964. eCollection 2015.

Abstract

Spinal muscular atrophy (SMA) is a monogenic neurodegenerative disorder subdivided into four different types. Whole genome methylation analysis revealed 40 CpG sites associated with genes that are significantly differentially methylated between SMA patients and healthy individuals of the same age. To investigate the contribution of methylation changes to SMA severity, we compared the methylation level of found CpG sites, designed as "targets", as well as the nearest CpG sites in regulatory regions of ARHGAP22, CDK2AP1, CHML, NCOR2, SLC23A2 and RPL9 in three groups of SMA patients. Of notable interest, compared to type I SMA male patients, the methylation level of a target CpG site and one nearby CpG site belonging to the 5'UTR of SLC23A2 were significantly hypomethylated 19-22% in type III-IV patients. In contrast to type I SMA male patients, type III-IV patients demonstrated a 16% decrease in the methylation levels of a target CpG site, belonging to the 5'UTR of NCOR2. To conclude, this study validates the data of our previous study and confirms significant methylation changes in the SLC23A2 and NCOR2 regulatory regions correlates with SMA severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Adolescent
  • Base Sequence
  • Case-Control Studies
  • Child, Preschool
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Nuclear Receptor Co-Repressor 2 / genetics*
  • Sodium-Coupled Vitamin C Transporters / genetics*
  • Spinal Muscular Atrophies of Childhood / genetics*

Substances

  • 5' Untranslated Regions
  • NCOR2 protein, human
  • Nuclear Receptor Co-Repressor 2
  • SLC23A2 protein, human
  • Sodium-Coupled Vitamin C Transporters

Grants and funding

HS is supported by the Swedish Research Council. GYZ is supported by the scholarship within the Swedish Institute Baltic Sea Region Exchange Program and Russian President Scholarship for study abroad. Funding from a Saint-Petersburg city administration is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.