GRIN2B promoter methylation deficits in early-onset schizophrenia and its association with cognitive function

Epigenomics. 2019 Feb;11(4):401-410. doi: 10.2217/epi-2018-0127. Epub 2019 Feb 20.

Abstract

Aim: We investigated GRIN1 and GRIN2B promoter methylation in first-episode schizophrenia patients compared with siblings and controls, testing for correlations between DNA methylation, cognitive performance and clinical variables.

Materials & methods: Blood-derived DNA from all groups underwent bisulfite conversion and pyrosequencing to determine methylation at CpG sites within the GRIN1 and GRIN2B promoters and results were compared with the measure of global methylation LINE-1.

Results: We found hypomethylation among all CpGs analyzed within GRIN2B promoter in patients and greater LINE-1 methylation in patients and siblings. CpG4 was correlated to a measure of intellectual function.

Conclusion: Changes in GRIN2B promoter methylation may represent an environmental influence contributing to glutamatergic dysfunction in psychosis and relate to lower cognitive performance in subjects with first-episode schizophrenia.

Keywords: DNA methylation; GRIN2B; LINE-1; cognition; first-episode psychosis; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Cognition
  • DNA Methylation*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Promoter Regions, Genetic*
  • Receptors, N-Methyl-D-Aspartate / genetics*
  • Schizophrenia / diagnosis
  • Schizophrenia / epidemiology
  • Schizophrenia / etiology*
  • Schizophrenic Psychology*
  • Young Adult

Substances

  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate