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Correction ARTICLE

Front. Genet., 14 August 2020 |

Corrigendum: DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia

Ju Gao1,2, Hongwei Yi3, Xiaowei Tang4, Xiaotang Feng5, Miao Yu1, Weiwei Sha4, Xiang Wang6, Xiaobin Zhang4 and Xiangrong Zhang1*
  • 1Department of Geriatric Psychiatry, Nanjing Brain Hospital, Affiliated to Nanjing Medical University, Nanjing, China
  • 2Centers of Disease Prevention and Control for Mental Disorders, Shanghai Changning Mental Health Center, Shanghai, China
  • 3Department of Pharmacology, School of Medicine, Southeast University, Nanjing, China
  • 4Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College, Yangzhou University, Yangzhou, China
  • 5Department of Psychiatry, Nanjing Qing Long Mountain Psychiatric Hospital, Nanjing, China
  • 6Medical Psychological Institute of the Second Xiangya Hospital, Central South University, Changsha, China

A Corrigendum on
DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia

by Gao, J., Yi, H., Tang, X., Feng, X., Yu, M., Sha, W., et al. (2018). Front. Genet. 9:646. doi: 10.3389/fgene.2018.00646

This corrigendum is to declare that the preliminary analysis of the data on MMP9 DNA methylation in the present article was published in the Letter to the Editor published in Schizophrenia Research. While the main focus, results and conclusions of the two papers differ, the data of MMP9 DNA methylation in Table 2 of the present article and the data in Figure 1B of the letter to editor in Schizophrenia Research represent essentially the same data, apart from a small difference in the numbers of cases. In order to avoid misinterpretation, we would like to add the citation of Gao et al. (2019) in the following places:

The Materials and Methods section, subsection MMP9 Expression and DNA Methylation Pyrosequencing Processing, pargraph 2:

“Genomic DNA was isolated from blood sample PBMCs using QIAamp DNA Blood Mini Kit (Qiagen, United States) and bisulfite-modified to convert unmethylated cytosine residues to uracil using EpiTec Fast DNA Bisulfite Kit (Qiagen, United States). PCR reactions were set up according to the instruction of PyroMark PCR Master Mix kit (Qiagen, Cat. No. 978703). In brief, gently mix 12.5 μl PyroMark PCR Master Mix, 2.5 μl CoralLoad Concentrate, 2 μl Primer, 6 μl RNase-free water and 2 μl template DNA. The thermal cycler is 95°C, 15 min; 94°C, 30 s, 56°C, 30 s, 72°C, 30 s, 45 cycles; 72°C, 10 min. After amplification, samples stored −20°C. Pyrosequencing was performed using the PyroMark Q96 ID System (Qiagen, United States) to analysis DNA methylation of MMP9 gene in patients and healthy controls. According to CpG islands track of UCSC genome Browser, we got the information that the human MMP9 gene contains four CpG islands. In view of that DNA methylation usually occurs within promoter or nearby exon regions intragenically, we chose the sequence on the first CpG island containing exons 4 and 5 for analysis. The region containing exon 4 using Hs_MMP9_02_PM PyroMarkCpG assay (Cat. No. PM00079198) analyzing sequence of 5′-GCCCCGGCATTCAGGGAGACGCCCATTTCGACGATGACGA-3′ and the region containing exon 5 using Hs_MMP9_01_PM PyroMark CpG assay (Cat. No. PM00079191) analyzing sequence of 5′-TCGGTTTGGAAACGCAGATGGCGCG-3′. Mean values of methylation of each exonic CpG-containing sequence were calculated. Totally, 9 CpG sites were included, naming CpG4-1, CpG4-2, CpG4-3, CpG4-4, CpG4-5, CpG5-1, CpG5-2, CpG5-3, and CpG5-4. The relative methylation changes of MMP9 of DS or NDS group patients were compared with the mean MMP9 methylation of healthy subjects (Gao et al., 2019).”

The Discussion section, paragraph 2:

“MMP9 has been considered to have pathological importance in patients with schizophrenia (Lepeta and Kaczmarek, 2015). Domenici et al. (2010) applied a focused proteomic approach in a large scale case-control study including 229 schizophrenic patients and 254 controls and revealed increased peripheral MMP9 in patients with schizophrenia. Similar results were reported by the recent ROC curve analysis (Ali et al., 2017) indicating that the increased MMP9 had some value in distinguishing schizophrenia and healthy controls. Increased peripheral MMP9 was also reported in remitted (Devanarayanan et al., 2015) and treatment-resistant schizophrenia (Yamamori et al., 2013). However, a few studies have shown negative findings of peripheral MMP9 in patients with schizophrenia, which had been attributed to disease state, medicine treatment (Kumarasinghe et al., 2013) or smoking status (Niitsu et al., 2014). For example, Kumarasinghe et al. (2013) found that MMP9 mRNA was significantly up-regulated in PBMCs of treatment-naïve schizophrenic patients than healthy subjects and returned to control level after 6–8 weeks antipsychotic pharmacotherapy of 200 mg/d CPZ-equivalents. Our study was consistent with the majority of the previous reports (Domenici et al., 2010; Devanarayanan et al., 2015; Ali et al., 2017) showing an increase MMP9 expression in PBMCs in these long-term stabilized patients with schizophrenia. This study along with our recent study (Gao et al., 2019) also indicated that MMP9 was significantly elevated in DS patients relative to NDS patients. As influencing factors including age, gender and smoking status were well matched, the increased MMP9 observed in the present study might reflect an association with clinical symptoms, especially the primary and persistent negative symptoms in DS patients compared with NDS patients.”

The authors apologize for not being able to accurately reference the Letter to the Editor due to the close publication date of the two articles and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.


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Keywords: deficit schizophrenia, matrix metalloproteinase-9, DNA methylation, gene expression, negative symptoms, pyrosequencing

Citation: Gao J, Yi H, Tang X, Feng X, Yu M, Sha W, Wang X, Zhang X and Zhang X (2020) Corrigendum: DNA Methylation and Gene Expression of Matrix Metalloproteinase 9 Gene in Deficit and Non-deficit Schizophrenia. Front. Genet. 11:823. doi: 10.3389/fgene.2020.00823

Received: 22 June 2020; Accepted: 08 July 2020;
Published: 14 August 2020.

Edited and reviewed by: Michael E. Symonds, University of Nottingham, United Kingdom

Copyright © 2020 Gao, Yi, Tang, Feng, Yu, Sha, Wang, Zhang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Xiangrong Zhang,

These authors have contributed equally to this work