DNA Methylation in Schizophrenia Subjects: Gender and MTHFR 677C/T Genotype Differences

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.

KEYWORDS::

• females
• folate
• metabolic syndrome
• methylation
• MTHFR
• schizophrenia

Financial & competing interests disclosure

This project was supported by the NIMH (grant number R01 MH082784-01) and the NIH-NCCR, GCRC Program (grant number UL1RR024986), the Chemistry Core of the Michigan Diabetes Research and Training Center (grant number NIH5P60 DK 20572), and the Washtenaw Community Health Organization. None of these funding and support agencies had any further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This project was supported by the NIMH (grant number R01 MH082784-01) and the NIH-NCCR, GCRC Program (grant number UL1RR024986), the Chemistry Core of the Michigan Diabetes Research and Training Center (grant number NIH5P60 DK 20572), and the Washtenaw Community Health Organization. None of these funding and support agencies had any further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.