Hypermethylation and increased expression of the DRD2 gene in schizophrenia

Abstract Background Schizophrenia (SCZ) is one of the most serious mental disorders, and dysfunction of the dopamine system is a key pathological hypothesis for SCZ. The DRD2 gene is a risk gene for SCZ, and its methylation is also considered an important marker of SCZ. Among methylation sites of A...

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Main Authors: Lili Qing, Tiantian Zou, Wensa Yin, Run Wu, Tiantian Cheng, Haodi Yuan, Chen Zhou, Xuanyu Chen, Jia Wang, Ting Yang, Liping Hu, Linlin Liu, Shengjie Nie
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-07154-y
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author Lili Qing
Tiantian Zou
Wensa Yin
Run Wu
Tiantian Cheng
Haodi Yuan
Chen Zhou
Xuanyu Chen
Jia Wang
Ting Yang
Liping Hu
Linlin Liu
Shengjie Nie
author_facet Lili Qing
Tiantian Zou
Wensa Yin
Run Wu
Tiantian Cheng
Haodi Yuan
Chen Zhou
Xuanyu Chen
Jia Wang
Ting Yang
Liping Hu
Linlin Liu
Shengjie Nie
author_sort Lili Qing
collection DOAJ
description Abstract Background Schizophrenia (SCZ) is one of the most serious mental disorders, and dysfunction of the dopamine system is a key pathological hypothesis for SCZ. The DRD2 gene is a risk gene for SCZ, and its methylation is also considered an important marker of SCZ. Among methylation sites of A total of 21 CpG sites were detected2, the CpG island upstream of exon 1 has been the most commonly studied. To our knowledge, CpG islands in other regions upstream of the start codon have not been studied. Methods MethylTarget was used to assess the methylation of 52 CpG sites in three regions of DRD2 exon 1 and intron 1, and ELISA was used to measure DRD2 protein levels. Results The methylation level of DRD2 as a whole and in the three assessed regions was significantly greater in the SCZ group than in the control group, and 26 of 52 CpG sites were significantly hypermethylated. When patients were divided by sex, 22 CpG sites with significant differences were identified in males, whereas only 2 CpG sites were identified in females by t test. After multiple testing correction, the statistical significance was attenuated for some loci. DRD2 expression in SCZ patients was lower than that in the control group. Conclusions These results suggest that hypermethylation and low expression of the DRD2 gene may be related to SCZ risk.
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spelling doaj-art-e531497ceb02431cbfe6684440950a3e2025-08-20T03:05:17ZengBMCBMC Psychiatry1471-244X2025-07-0125111210.1186/s12888-025-07154-yHypermethylation and increased expression of the DRD2 gene in schizophreniaLili Qing0Tiantian Zou1Wensa Yin2Run Wu3Tiantian Cheng4Haodi Yuan5Chen Zhou6Xuanyu Chen7Jia Wang8Ting Yang9Liping Hu10Linlin Liu11Shengjie Nie12NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityDept. of Medical, Mental Hospital of Yunnan Province, Mental Health Center Affiliated with Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityNHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical UniversityAbstract Background Schizophrenia (SCZ) is one of the most serious mental disorders, and dysfunction of the dopamine system is a key pathological hypothesis for SCZ. The DRD2 gene is a risk gene for SCZ, and its methylation is also considered an important marker of SCZ. Among methylation sites of A total of 21 CpG sites were detected2, the CpG island upstream of exon 1 has been the most commonly studied. To our knowledge, CpG islands in other regions upstream of the start codon have not been studied. Methods MethylTarget was used to assess the methylation of 52 CpG sites in three regions of DRD2 exon 1 and intron 1, and ELISA was used to measure DRD2 protein levels. Results The methylation level of DRD2 as a whole and in the three assessed regions was significantly greater in the SCZ group than in the control group, and 26 of 52 CpG sites were significantly hypermethylated. When patients were divided by sex, 22 CpG sites with significant differences were identified in males, whereas only 2 CpG sites were identified in females by t test. After multiple testing correction, the statistical significance was attenuated for some loci. DRD2 expression in SCZ patients was lower than that in the control group. Conclusions These results suggest that hypermethylation and low expression of the DRD2 gene may be related to SCZ risk.https://doi.org/10.1186/s12888-025-07154-ySchizophreniaDRD2 geneDNA methylationGene expression
spellingShingle Lili Qing
Tiantian Zou
Wensa Yin
Run Wu
Tiantian Cheng
Haodi Yuan
Chen Zhou
Xuanyu Chen
Jia Wang
Ting Yang
Liping Hu
Linlin Liu
Shengjie Nie
Hypermethylation and increased expression of the DRD2 gene in schizophrenia
BMC Psychiatry
Schizophrenia
DRD2 gene
DNA methylation
Gene expression
title Hypermethylation and increased expression of the DRD2 gene in schizophrenia
title_full Hypermethylation and increased expression of the DRD2 gene in schizophrenia
title_fullStr Hypermethylation and increased expression of the DRD2 gene in schizophrenia
title_full_unstemmed Hypermethylation and increased expression of the DRD2 gene in schizophrenia
title_short Hypermethylation and increased expression of the DRD2 gene in schizophrenia
title_sort hypermethylation and increased expression of the drd2 gene in schizophrenia
topic Schizophrenia
DRD2 gene
DNA methylation
Gene expression
url https://doi.org/10.1186/s12888-025-07154-y
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