DNA methylation in schizophrenia subjects: gender and MTHFR 677C/T genotype differences.
OBJECTIVE
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%).


CONCLUSIONS
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.
College of Pharmacy, Department of Clinical Social & Administrative Sciences, University of Michigan, 428 Church Street, Ann Arbor, MI 48109, USA.
Kyle J
KJ
Burghardt
J Richard
JR
Pilsner
Michael J
MJ
Bly
Vicki L
VL
Ellingrod
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002746:Chlorpromazine / Q000008:administration & dosage / Q000627:therapeutic use; D019175:DNA Methylation / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D058889:Molecular Typing; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors
D014150:Antipsychotic Agents; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002746:Chlorpromazine