DNA Methylation Pattern of Gene Promoters of MB-COMT, DRD2, and NR3C1 in Turkish Patients Diagnosed with Schizophrenia
Hasan Mervan Aytac 1*, Yasemin Oyaci 2, Mustafa Pehlivan 3, Sacide Pehlivan 2
1Department of Psychiatry, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey, 2Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Turkey, 3Department of Hematology, Gaziantep University, Faculty of Medicine, Gaziantep, Turkey
Received: May 4, 2021; Revised: June 12, 2021; Accepted: June 14, 2021; Published online: June 14, 2021.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Objective: Genetics alone can not explain the etiopathology of schizophrenia (SCZ). It is well-known that environmental risk factors exposed during early development and young adulthood also contribute to SCZ in susceptible individuals. We aim to evaluate the methylation status of membrane-bound catechol-O-methyltransferase (MB-COMT) promotor, dopamine receptor D2 (DRD2), and nuclear receptor subfamily 3 group C member 1 (NR3C1) gene in patients with SCZ by comparing healthy controls.
Methods: A sample of 110 patients with SCZ and 100 age- and sex-matched healthy volunteers was included in the study. The interview was started by filling out data forms that included sociodemographic and clinical information. SCID-I was used to confirming the diagnosis according to DSM-IV-TR criteria. The patients were evaluated with PANSS in terms of symptom severity. MSP-PCR was used to determine the methylation status of MB-COMT promotor, DRD2, and NR3C1 gene from DNA material.
Results: When we compared the percentages of MB-COMT promotor, DRD2, and NR3C1 gene methylation status in SCZ patients with the healthy control group, the percentages of MB-COMT promotor (OR: 0.466; 95% Cl: 0.268–0.809; p=.006), DRD2 (OR: 0.439; 95% Cl: 0.375–0.514; p<.001), and NR3C1 (OR: 0.003; 95% Cl: 0.001–0.011; p<.001) gene methylation status of SCZ was found to be significantly different from the control group. Whereas unmethylation of MB-COMT promotor and NR3C1 genes were associated with SCZ, the partial methylation of the DRD2 gene was related to the SCZ.
Conclusion: The MB-COMT promotor, DRD2, and NR3C1 gene methylation status may be associated with the SCZ in the Turkish population.
Keywords: Schizophrenia, COMT, DRD2, NR3C1, DNA methylation, epigenetics, methylation-specific polymerase chain reaction