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.

Genetics of second-generation antipsychotic and mood stabilizer-induced weight gain in bipolar disorder

“…MTHFR-mediated methylation may contribute towards the onset of AIWG [73]. Previous studies have found evidence of an association between AIWG/antipsychotic-induced metabolic syndrome and rs1801131 [72,74], whereas we found a nominal association between weight gain and rs17367504 (only 8 kbp from rs1801131) in the SGAP-treated group and rs1133398 (40 kbp from rs1801131) both in the MS-treated group and in the combined-treatment group.…”

Overcoming artefact: anticipation in 284 Portuguese kindreds with familial amyloid polyneuropathy (FAP) ATTRV30M

“…Furthermore, increasing evidence has been showing that epigenetic mechanisms are involved in age-related traits and in gender differences. For instance, DNA methylation has been associated with particular genotypes in the female group in a study of schizophrenia 27. There is now a consensus that studies should focus on epigenetic biomarkers and their interaction with DNA and environment 28.…”

Antipsychotic Induced Weight Gain: Genetics, Epigenetics, and Biomarkers Reviewed

“…Burghardt et al (2012) studied the MTHFR C677T (rs1801133) variant with Long Interspersed Nucleotide Element 1 (LINE-1) DNA methylation, an index of global methylation levels, in 133 patients with schizophrenic disorders. They reported a significant interaction between gender, MTHFR C677T genotype, and overall global methylation.…”

“…They reported a significant interaction between gender, MTHFR C677T genotype, and overall global methylation. Females who were homozygous for the T allele had the lowest methylation compared to other groups [58]. Another study by Lott et al (2013) analyzed the relationship between COMT promoter methylation and metabolic syndrome in 86 schizophrenia patients treated with atypical antipsychotics.…”