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

• Published in: Epigenomics Vol. 4; no. 3; pp. 261 - 268
• Main Authors: Burghardt, Kyle J, Pilsner, J Richard, Bly, Michael J, Ellingrod, Vicki L
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.06.2012
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - therapeutic use; Care and treatment; Chlorpromazine - administration & dosage; Chlorpromazine - therapeutic use; Dietary supplements; DNA methylation; DNA Methylation - genetics; DNA Mutational Analysis; Fasting; Female; Folic acid; Folic Acid - metabolism; Genetic aspects; Genotype; Genotypes; Humans; Identification and classification; Long Interspersed Nucleotide Elements - genetics; Male; Mental disorders; Metabolic disorders; Metabolic Syndrome - complications; Metabolic Syndrome - drug therapy; Metabolic Syndrome - genetics; Metabolic Syndrome - metabolism; Methylation; Methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; Middle Aged; Molecular Typing; Polymorphism, Single Nucleotide; Schizophrenia; Schizophrenia - complications; Schizophrenia - drug therapy; Schizophrenia - genetics; Schizophrenia - metabolism; Sex differences; Sex Factors; United States
• ISSN: 1750-1911; 1750-192X; 1750-192X
• DOI: 10.2217/epi.12.25

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. 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. 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%). 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.