Low methylation rates of dopamine receptor D2 gene promoter sites in Japanese schizophrenia subjects.
According to the dopamine hypothesis, several studies on the gene for the dopamine receptor D2 (DRD2) have been conducted. However, no trait biomarkers on DRD2 are available. We examined whether the methylation rates in the upstream region of DRD2 in leukocytes are different in schizophrenia (SCZ) subjects compared to control subjects.



We selected seven CpG sites in the upstream region of DRD2 that may theoretically bind major transcription factors. The methylation rates in these regions of 50 medicated and 18 drug-naïve SCZ subjects were compared with those of age-matched control subjects.



The methylation rates were significantly lower in medicated (CpG2, P < 0.0001; CpG4, P = 0.013; CpG7, P < 0.0001; and average: 12.9 ± 1.8 vs. 14.1 ± 2.2, P = 0.005) and drug-naïve SCZ subjects (CpG1, P = 0.006; CpG2, P = 0.001; CpG3, P = 0.001; CpG5, P = 0.02; CpG6, P = 0.015; CpG7, P = 0.027; and average: 9.86 ± 0.9 vs. 11.2 ± 1.3, P = 0.002).



We confirmed low methylation rates in the upstream region of DRD2 in both medicated and drug-naïve SCZ subjects. Low methylation rates of DRD2 in leukocytes may be a trait biomarker for SCZ.
a Department of Neuropsychiatry, Molecules and Function , Ehime University Graduate School of Medicine , Toon , Ehime , Japan ;
Yuta
Y
Yoshino
a Department of Neuropsychiatry, Molecules and Function , Ehime University Graduate School of Medicine , Toon , Ehime , Japan ;
Kentaro
K
Kawabe
a Department of Neuropsychiatry, Molecules and Function , Ehime University Graduate School of Medicine , Toon , Ehime , Japan ;
Takaaki
T
Mori
a Department of Neuropsychiatry, Molecules and Function , Ehime University Graduate School of Medicine , Toon , Ehime , Japan ;
Yoko
Y
Mori
a Department of Neuropsychiatry, Molecules and Function , Ehime University Graduate School of Medicine , Toon , Ehime , Japan ;
Kiyohiro
K
Yamazaki
b Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences , The University of Tokushima Graduate School , Tokushima , Japan.
Shusuke
S
Numata
a Department of Neuropsychiatry, Molecules and Function , Ehime University Graduate School of Medicine , Toon , Ehime , Japan ;
Shunsuke
S
Nakata
a Department of Neuropsychiatry, Molecules and Function , Ehime University Graduate School of Medicine , Toon , Ehime , Japan ;
Taku
T
Yoshida
a Department of Neuropsychiatry, Molecules and Function , Ehime University Graduate School of Medicine , Toon , Ehime , Japan ;
Jun-Ichi
J
Iga
b Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences , The University of Tokushima Graduate School , Tokushima , Japan.
Tetsuro
T
Ohmori
a Department of Neuropsychiatry, Molecules and Function , Ehime University Graduate School of Medicine , Toon , Ehime , Japan ;
Shu-Ichi
S
Ueno
D000328:Adult; D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D019175:DNA Methylation; D016002:Discriminant Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2
Biomarker; dopamine receptor D2 gene; methylation; pyrosequencer; schizophrenia