DNA methylation in schizophrenia subjects: gender and MTHFR 677C/T genotype differences

Epigenomics. 2012 Jun;4(3):261-8. doi: 10.2217/epi.12.25.

Abstract

Aim: In schizophrenia, metabolic syndrome incidence is double that of the general population, with women having a higher incidence. Pharmacogenetically regulated folic acid may be related to this risk. DNA methylation and metabolic syndrome within this group has not been previously studied.

Methods: Metabolic syndrome was evaluated with fasting laboratory measurements, and dietary and lifestyle assessments. Methylation analysis used a peripheral sample for the LINE-1 assay. DNA was also genotyped for MTHFR 677C/T.

Results: This analysis included 133 subjects. We found a significant relationship between LINE-1 methylation, and an interaction between MTHFR and gender, controlling for serum folate (p = 0.008). Females with the 677TT genotype had the lowest methylation (56%) compared with the other groups (75%).

Conclusion: TT genotype females had the lowest methylation, which may explain metabolic syndrome gender differences in schizophrenia. Folate supplementation may be a suggested intervention within schizophrenia; however, additional work is required.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / therapeutic use
  • Chlorpromazine / administration & dosage
  • Chlorpromazine / therapeutic use
  • DNA Methylation / genetics*
  • DNA Mutational Analysis
  • Female
  • Folic Acid / metabolism*
  • Genotype
  • Humans
  • Long Interspersed Nucleotide Elements / genetics
  • Male
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / metabolism
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Middle Aged
  • Molecular Typing
  • Polymorphism, Single Nucleotide*
  • Schizophrenia / complications
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*
  • Schizophrenia / metabolism
  • Sex Factors

Substances

  • Antipsychotic Agents
  • Folic Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Chlorpromazine