AUTHOR=Yoshino Yuta , Ozaki Yuki , Yamazaki Kiyohiro , Sao Tomoko , Mori Yoko , Ochi Shinichiro , Iga Jun-ichi , Ueno Shu-ichi 

TITLE=DNA Methylation Changes in Intron 1 of Triggering Receptor Expressed on Myeloid Cell 2 in Japanese Schizophrenia Subjects

JOURNAL=Frontiers in Neuroscience

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2017.00275

DOI=10.3389/fnins.2017.00275

ISSN=1662-453X

ABSTRACT=<p>A hypothesis for schizophrenia (SCZ) called the “microglia hypothesis” has been suggested. In SCZ, expression of <italic>triggering receptor expressed on myeloid cell 2</italic> (<italic>TREM2</italic>) mRNA is higher in leukocytes than in healthy individuals. Here, the methylation rates of four CpG sites in <italic>TREM2</italic> intron 1 that may bind important transcription factors and the correlation between the methylation rate and mRNA expression were determined. We compared the methylation rates in SCZ patients and age-matched controls (<italic>n</italic> = 50 each). SCZ patients had significantly lower methylation rates of CpG 2 (17.0 ± 6.7 vs. 20.2 ± 5.0; <italic>p</italic> = 0.02) and CpG 3 (23.8 ± 8.2 vs. 28.1 ± 6.2; <italic>p</italic> = 0.01). The average methylation rate (15.3 ± 5.2 vs. 17.6 ± 3.9; <italic>p</italic> = 0.009) was also lower. A significant negative correlation was found between <italic>TREM2</italic> mRNA expression and the methylation rate of CpG 2 (<italic>r</italic> = −0.252, <italic>p</italic> = 0.012). SCZ susceptibility markers may include low methylation at <italic>TREM2</italic> intron 1 and increased <italic>TREM2</italic> mRNA levels. Our pilot study requires validation with higher numbers of participants and with other myeloid cell types.</p>